BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnos...BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnosis.METHODS The study cohort comprised 50 patients diagnosed with GC and 50 healthy control subjects.A panel of 7 pro-inflammatory cytokines,including interleukin(IL)-1β,IL-2,IL-6,IL-8,IL-12,tumor necrosis factor-α,and interferon-γ(IFN-γ)were quantified using multiplex Luminex assays.Comparative analyses were conducted to evaluate cytokine levels between the GC patients and healthy controls.The diagnostic potential of serum pro-inflammatory cytokines in differentiating GC patients from healthy individuals was assessed through receiver operating characteristic(ROC)curve analysis.The correlation between serum cytokine levels and disease severity,as classified by the tumor-node-metastasis staging system,was analyzed using Spearman's rank correlation coefficient.RESULTS In comparison to the control group,patients with GC demonstrated significantly elevated serum levels of IL-1β(t=-4.089,P<0.001),IL-6(t=-3.983,P<0.001),IL8(t=-5.460,P<0.001),and IFN-γ(t=-2.856,P=0.005).ROC curve analysis indicated that the area under the curve values for IL-1β,IL-6,and IL-8 exceeded 0.7,effectively distinguishing GC patients from healthy controls.Additionally,serum levels of IL-1β(r=0.424,P=0.012)and IL-6(r=0.742,P<0.001)were positively correlated with the T stage in GC patients.Similarly,serum concentrations of IL-1β(r=0.356,P=0.039)and IL-6(r=0.441,P=0.008)exhibited a positive association with the N stage in these patients.CONCLUSION These findings suggest that circulating pro-inflammatory cytokines,such as IL-1β,IL-6,and IL-8,may serve as potential biomarkers for the diagnosis of GC.展开更多
This editorial critically analyses the recent article by Jung et al,which investigates the utility of 4-hour serum amylase and lipase as early blood markers for postendoscopic retrograde cholangiopancreatography(ERCP)...This editorial critically analyses the recent article by Jung et al,which investigates the utility of 4-hour serum amylase and lipase as early blood markers for postendoscopic retrograde cholangiopancreatography(ERCP)acute pancreatitis prediction.Although these enzymes are valuable for the early diagnosis of post-ERCP pancreatitis,they lack specificity for disease etiology and provide limited insight into the molecular mechanisms underlying disease progression.Several cytokines,notably interleukin(IL)-6,tumor necrosis factor-alpha,and IL-8,are increased in post-ERCP pancreatitis and may serve as potential predictors for disease severity.The incorporation of these biomarkers in early enzymatic biomarkers and established prognostic scoring systems could further enhance their accuracy and allow for earlier,more effective management of patients with post-ERCP pancreatitis.展开更多
While viral infections can disturb the host gut microbiome,the dynamic alterations in microbial composition following infection remain poorly characterized.This study identified SRV-8-infected monkeys and classified t...While viral infections can disturb the host gut microbiome,the dynamic alterations in microbial composition following infection remain poorly characterized.This study identified SRV-8-infected monkeys and classified them into five groups based on infection progression.16S rRNA amplicon sequencing revealed significant alterations in the relative and inferred absolute abundance of bacterial genera UCG-002,Agathobacter,Coprococcus,and Holdemanella during the early stage of SRV-8 infection,coinciding with provirus formation.These microbial shifts were accompanied by functional modifications in bacterial communities at the same stage.In contrast,ITS amplicon sequencing indicated no significant differences in fungal composition between healthy wild-type and SRV-8-infected monkeys.Spearman correlation analyses demonstrated close interactions between intestinal bacteria and fungi following SRV-8 infection.Additionally,SRV-8 seropositive groups exhibited significantly elevated mRNA expression levels of pro-inflammatory(TNF-α,IFN-γ,IL-1β,and IL-6)and anti-inflammatory(IL-10)cytokine genes,highlighting close associations between inflammatory cytokines and immune responses.Overall,these findings provide a comprehensive characterization of bacterial and fungal microbiota dynamics and inflammatory cytokine responses associated with SRV-8 infection,clarifying the pathobiological mechanisms underlying SRV-8 infection from the perspective of the gut microbiome.展开更多
Anti-inflammatory activity ofRubus idaeus L. and possible mechanisms involved were explored in lipopolysaccharide （LPS）-treated RAW 264.7 cells. The effects of ethanol extract of R. idaeus on the levels of pro-infla...Anti-inflammatory activity ofRubus idaeus L. and possible mechanisms involved were explored in lipopolysaccharide （LPS）-treated RAW 264.7 cells. The effects of ethanol extract of R. idaeus on the levels of pro-inflammatory cytokines, including tumor necrosis factor-alfa （TNF-α）, interleukin-6 （IL-6） and interleukin-1 beta （IL-1β）, as well as pro-inflammatory mediators, such as nitric oxide （NO）, inducible nitric oxide synthase （iNOS） and cyclooxygenase-2 （COX-2） were studied by Sandwich ELISA, real-time PCR, and Western blot analysis. Moreover, the effects of ethanol extract of R. idaeus on anti-inflammatory cytokine interleukin-10 （IL-10） and anti-inflammatory mediator heme oxygenase-1 （HO-1） were also investigated using the same methods. Furthermore, nuclear factor-gB （NF-κB） level was assayed by immunocytochemistry. The results showed that the production of IL-1β, IL-6, NO, TNF-α and COX-2 in LPS-treated cells could be significantly inhibited （P〈0.01 or P〈0.05） by ethanol extract ofR. idaeus compared with that in the cells treated with LPS only. Meanwhile, the production of NF-r,B was also inhibited by the extract. Based on these results, the anti-inflammatory activity ofR. idaeus was attributed to the down-regulation of IL-6, IL-1β and TNF-α levels as well as gene expression of iNOS and COX-2 through the suppression of NF-κB activation, and induction of anti-inflammatory cytokine IL- 10 and anti-inflammatory mediator HO- 1.展开更多
Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degen...Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflammatory cytokines that upregulate and downregulate, respectively, the production of inflammatory mediators. While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages, anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines, thus determining the end of the process. In this review, we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration. In particular, we focus on interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-β, interleukin-10 and transforming growth factor-β.展开更多
BACKGROUND The pathogenesis of cognitive impairment in schizophrenia(SCZ)remains unclear.Accumulating studies showed that inflammatory-immune dysregulation and altered brain derived neurotrophic factor(BDNF)levels pla...BACKGROUND The pathogenesis of cognitive impairment in schizophrenia(SCZ)remains unclear.Accumulating studies showed that inflammatory-immune dysregulation and altered brain derived neurotrophic factor(BDNF)levels play a crucial role in the psychopathology of SCZ.However,their association with cognitive dysfunction in first-episode SCZ patients has not been thoroughly investigated.AIM To explore the interaction effects between cognitive function and inflammatory cytokines and BDNF in first-episode SCZ.METHODS The current study is a cross-sectional case-control investigation that recruited 84 patients with first-episode SCZ(SCZ group)and 80 healthy controls(HCs group)at the Huzhou Third Municipal Hospital between August 2021 and September 2023.ELISA was employed to measure the serum levels of interleukin(IL)-1β,IL-4,IL-6,IL-10,and BDNF.The Chinese brief cognitive test(C-BCT)and the positive and negative syndrome scales were measured the severity of cognitive impairment and psychiatric symptoms.RESULTS Compared to the HC group,the SCZ group exhibited elevated IL-1βand IL-6 levels,decreased BDNF levels,and reduced C-BCT scores(all P<0.001).In SCZ,BDNF was negatively correlated with IL-6(r=-0.324,P<0.05).Information processing speed was negatively correlated with IL-6(r=-0.315,P<0.05)and positively with BDNF(r=0.290,P<0.05);attention,working memory,comprehensive ability,and executive function were negatively correlated with IL-1βand IL-6(all P<0.05)and positively with BDNF(all P<0.05).Multiple regression analysis showed IL-6 influenced C-BCT dimensions(β=-0.218 to-0.327,all P<0.05);attention and executive ability were influenced by IL-1β(β=-0.199 to-0.261,all P<0.05);comprehensive executive ability was influenced by BDNF(β=0.209,P<0.05).CONCLUSION Our findings suggested that interrelationships between immune dysfunction and neurotrophic deficiency might underlie the pathological mechanisms of cognitive impairments in first-episode SCZ patients.展开更多
Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), rep- resents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with...Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), rep- resents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with a relapsing and remitting clinical course. Mucosal mac- rophages play an important role in the mucosal im- mune system, and an increase in the number of newly recruited monocytes and activated macrophages has been noted in the inflamed gut of patients with IBD. Activated macrophages are thought to be major con- tributors to the production of inflammatory cytokines in the gut, and imbalance of cytokines is contributing to the pathogenesis of IBD. The intestinal inflammation in IBD is controlled by a complex interplay of innate and adaptive immune mechanisms. Cytokines play a key role in IBD that determine T cell differentiation of Th1, Th2, T regulatory and newly described Th17 cells. Cytokines levels in time and space orchestrate the development, recurrence and exacerbation of the inflammatory process in IBD. Therefore, several cyto- kine therapies have been developed and tested for the treatment of IBD patients.展开更多
Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of N...Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.展开更多
AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated fro...AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.展开更多
AIM:To observe the effect of acupuncture and moxibustion on the expression of IL-1beta and IL-6 mRNA in ulcerative colitis rats.METHODS:The SD rat ulcerative colitis model was created by immunological method associate...AIM:To observe the effect of acupuncture and moxibustion on the expression of IL-1beta and IL-6 mRNA in ulcerative colitis rats.METHODS:The SD rat ulcerative colitis model was created by immunological method associated with local stimulation. Colonic mucosa was prepared from human fresh surgical colonic specimens, homogenized by adding appropriate amount of normal saline and centrifuged at 3000r/min. The supernatant was collected for measurement of protein conentration and then mixed with Freund adjuvant. This antigen fluid was first injected into the plantae of the model group rats, and then into their plantae, dorsa, inguina and abdominal cavities (noFreund adjuvant for the last injection) again on the 10th, 17th, 24th and 31st day. When a certain titer of serum anti colonic antibody was reached, 2% formalin and antigen fluid (no Freund adjuvant) were administered separately by enema. The ulcerative colitis rat model was thus set up. The animals were randomly divided into four groups: model control group (MC, n = 8), electro acupuncture group (EA, n = 8), herbs partition moxibustion group (HPM 8), normal control group (NC,n = 8). HPM: Moxa cones made of refined mugwort floss were placed on the medicinal pad (medicinal pad dispensing: Radix Aconiti praeparata, cortex Cinnamomi, etc) for Qihai (RN 6) and Tianshu (ST 25, bilateral) and ignited. Two moxa cones were used for each acupoint once a day and 14 times in all. EA: Tianshu (bilateral) and Qihai were stimulated by the intermittent pulse with 2Hz frequency, 4mA intensity for 20 minutes once a day and 14 times in all. After treatment, rats of all four groups were killed simultaneously. The spleen was separated and the distal colon was dissected. Total tissue RNA was isolated by the guanidinium thiocyanate phenol chloroform extraction method. RT-PCR technique was used to study the expression of IL-1 beta and IL-6 mRNA.RESULTS:IL-1 beta and IL-6 mRNAs were not detected in the spleen and colonic mucosa of the NC rats, whereas they were significantly expressed in that of the MC rats.IL-1 beta and IL-6 mRNAs were markedly lower in the EA and HPM rats than that in MC rats. There was no significant difference between the levels of IL-1 beta and IL-6 mRNAs in the EA and HPM rats. The expressions of IL-1 beta and IL-6 mRNAs were nearly the same in the spleen and colon of all groups.CONCLUSION:Acupuncture and moxibustion greatly inhibited the expression of IL-1 beta and IL-6 mRNA in the experimental ulcerative colitis rats.展开更多
AIM： To investigate the correlation between the antifibrotic effect of baicalin and serum cytokine production in rat hepatic fibrosis, METHODS： Forty male Sprague-Dawley rats were divided randomly into four groups：...AIM： To investigate the correlation between the antifibrotic effect of baicalin and serum cytokine production in rat hepatic fibrosis, METHODS： Forty male Sprague-Dawley rats were divided randomly into four groups： normal control group, model group, baicalin-treated group, and colchicine-treated group. Except for the normal control group, all rats in the other groups were administered with carbon tetrachloride to induce hepatic fibrosis. At the same time, the last two groups were also treated with baicalin or colchicine. At the end of the 8 wk, all animals were sacrificed. Serum alanine aminotransferase （ALl＇）, aspartate aminotransferase （AST）, transforming growth factor （TGF）-β1, tumor necrosis factor （TNF）-α, interleukin （IL）-6 and IL-10 were measured. Liver index, hepatic hydroxyproline content and the degree of liver fibrosis were also evaluated. RESULTS： The levels of ALT, AST and liver index in the baicalin-treated group were markedly lower than those in the model group （ALT： 143.88 ± 14.55 U/L vs 193.58± 24.35 U/L; AST： 263.66 ± 44.23 U/L vs 404.37± 68.29 U/L; liver index： 0.033 ± 0.005 vs 0.049± 0.009, P 〈 0.01）. Baicalin therapy also significantly attenuated the degree of hepatic fibrosis, collagen area and collagen area percentage in liver tissue （P 〈 0.01）. Furthermore, the levels of serum TGF-β1, TNF-α and IL-6 were strikingly reduced in the baicalin-treated group compared with the model group, while the production of IL-10 was up-regulated： （TGF-β1：260.21 ± 31.01 pg/mL vs 375.49 ± 57.47 pg/mL; TNF-α： 193.40±15.18 pg/mL vs 260.04 ± 37.70 pg/mL; IL-α：339.87 ± 72.95 pg/mL vs 606.47 ± 130.73 pg/mL; IL-10：506.22 ± 112.07 pg/mL vs 316.95 ± 62.74 pg/mL, P 〈 0.01）. CONCLUSION： Baicalin shows certain therapeutic effects on hepatic fibrosis, probably by immunoregulating the imbalance between profibrotic and antifibrotic cytokines.展开更多
AIM: To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic hypotension and cytokine production in lipopolysaccharide (LPS)-induced endotoxic shock (ES) rats. METHODS: The changes of blood pressure wer...AIM: To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic hypotension and cytokine production in lipopolysaccharide (LPS)-induced endotoxic shock (ES) rats. METHODS: The changes of blood pressure were observed using physiological record instrument in four groups of rats: LPS (8mg.kg(-1),iv) induced ES; CCK-8 (40 microg.kg(-1), iv) pretreatment 10 min before LPS (8mg.kg(-1)); CCK-8 (40 micro.kg(-1), iv) or normal saline (control) groups. Differences in tissue and circulating specificity of the proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6) were assayed with ELISA kits. RESULTS: CCK-8 reversed LPS-induced decrease of mean artery blood pressure (MABP) in rats. Compared with control, LPS elevated the serum level of IL-6 significantly (3567 +/- 687 ng.L(-1) vs 128 +/- 22 ng.L(-1), P【0.01), while contents of TNF-alpha and IL-1beta elevated significantly (277 +/- 86 ng.L(-1) vs not detectable and 43 +/- 9 ng.L(-1) vsnot detectable, P【0.01) but less extent than IL-6. CCK-8 significantly inhibited the LPS-induced increase in serum TNF-alpha IL-1beta and IL-6. LPS elevated spleen and lung content of IL-1beta significantly (5184 +/- 85 ng.L(-1) vs 1047 +/- 21 ng.L(-1) and 4050 +/- 614 ng.L(-1) vs not detectable, P【0.01), while levels of TNF-alpha and IL-6 also rose significantly but in less extent than IL-1beta. CCK-8 inhibited the LPS-induced increase of the cytokines in spleen and lung. In the heart, CCK-8 significantly inhibited LPS-induced increase of TNF-alpha (864 +/- 123 ng.L(-1) in CCK-8+LPS group vs 1599 +/- 227 ng.L(-1) in LPS group, P 【 0.01), and IL-1beta (282 +/- 93 ng.L(-1) in CCK-8+LPS group vs 621 +/- 145ng.L(-1) in LPS group, P 【 0.01). CONCLUSION: CCK-8 reverses ES, which may be related to its inhibitory effect on the overproduction of cytokines.展开更多
Abstract AIM To investigate whether PMN from patients with IBD or infectious colitis, respectively, secrete increased amounts of pro inflammatory cytokines and can be regulated by IL 10. METHODS Secretion (E...Abstract AIM To investigate whether PMN from patients with IBD or infectious colitis, respectively, secrete increased amounts of pro inflammatory cytokines and can be regulated by IL 10. METHODS Secretion (ELISA) as well as corresponding mRNA levels (semiquantitative RT PCR) of pro inflammatory cytokines (IL 1β, TNF α) and of IL 1 receptor antagonist were assessed in peripheral PMN. RESULTS PMN from patients with IBD are primed to secrete enhanced amounts of pro inflammatory cytokines accompanied by detection of corresponding mRNAs in comparison with normal controls. This finding is not specific for IBD but rather reflects intestinal inflammation in general. IL 10 markedly inhibited proinflammatory cytokine secretion as well as corresponding mRNA concentrations. CONCLUSION PMN are an important source of pro inflammatory cytokines in patients with intestinal inflammation and can be downregulated by IL 10.展开更多
AIM: To investigate the biliary biochemical constituents and cytokines in infantile hepatitis syndrome (IHS). METHODS: From 42 IHS subjects and 21 controls, serum and biliary biochemical constituents, including total ...AIM: To investigate the biliary biochemical constituents and cytokines in infantile hepatitis syndrome (IHS). METHODS: From 42 IHS subjects and 21 controls, serum and biliary biochemical constituents, including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GT), total bile acid (TBA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) both in bile and serum, were assayed. The subjects with IHS were divided into a cholestasis group (n = 21) and a hepatitis group (n = 21). RESULTS: In the cholestasis group, serum TBIL, DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01); and also the biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control, whereas biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the cholestasis group, serum IL-6 and TNF-α levels were lower than those in bile (P < 0.01). In the hepatitis group, serum DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01 or 140.57 ± 70.32 vs 79.06 ± 35.25, P < 0.05), while biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control (P < 0.01), and biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the hepatitis group, serum IL-6 and TNF-α levels were also lower than those in bile (P < 0.01). Serum TBIL, DBIL, γ-GT, IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitis group, while biliary IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitisgroup. Biliary IL-6 and TNF-α were found to be more significantly increased than serum IL-6 and TNF-α in IHS (P < 0.01). The biliary IL-6 and TNF-α levels were positively correlated with serum DBIL, TBA and γ-GT levels in IHS subjects. CONCLUSION: Biliary biochemical constituents alter in coincidence with pathological changes in hepatocellular injury. Cholestasis is more serious in IHS patients of cholestasis subtype. Assay of biliary IL-6 and TNF-α levels can be specific and sensitive to determine the inflammatory status of impaired liver in IHS.展开更多
Gene therapy offers a new approach for treatment of cancer. Transfer of genes encoding immunostimulatory cytokines has been used with remarkable success to eliminate cancer in animals. However, clinical trials in pati...Gene therapy offers a new approach for treatment of cancer. Transfer of genes encoding immunostimulatory cytokines has been used with remarkable success to eliminate cancer in animals. However, clinical trials in patients with this strategy had limited efficacy. Therefore, improvement ofgene transfer vector system is necessary. A hybrid viral vector, consisting of SFV replicon with either murine IL-12 or reporter LacZ gene, was constructed. This hybrid vector showed specificity and high level of expression in HCC both in vitro and in vivo. In a rat orthotropic liver tumor model, treatment of established tumors by the hybrid vector with raiL- 12 gene resulted in a strong anti-tumor activity without accompanying toxicity. Subsequently, a helper-dependent adenovirus vectors containing a mifepristone （RU486） inducible system was constructed for controlled and liver-specific expression of human interleukin 12 （hIL- 12） （HD-Ad/RUhIL- 12） and mouse IL-12 （mIL-12） （HD-Ad/RUmIL-12）. Data showed that high and sustained serum levels of hlL-12 could be attained by continuing administration of RU486 every 12 or 24 h. Repetitive induction ofhlL-12 could be obtained over, at least, a period of 48 weeks after a single injection of HD-Ad/RUhlL-12. Treatment of liver metastases with of HD-Ad/RUmIL- 12 plus RU846 resulted in complete tumor regression in all animals. Then, different cytokine genes were inserted into conditional replicative adenoviruses vectors （also called oncolytic adenovirus）. Replication ofadenovirus in tumor cells would kill tumor cells and release viruses, which infect surrounding tumor cells. The combination of cytopathic effect by oncolytic adenovirus and biological effect of transgene would exert strong antitumor activity. These new types of vectors may provide a potent and safe tool for cancer gene therapy.展开更多
Osteoarthritis(OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show bio...Osteoarthritis(OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show biochemical changes within joint tissue which can occur many years before symptoms become apparent. The need for better diagnostic and prognostic tools is heightened with the prevalence of OA set to increase in aging and obese populations. As inflammation is increasingly beingconsidered an important part of OAs pathophysiology, cytokines are being assessed as possible candidates for biochemical markers. Cytokines, both pro- and antiinflammatory, as well as angiogenic and chemotactic, have in recent years been studied for relevant characteristics. Biochemical markers show promise in determination of the severity of disease in addition to monitoring of the efficacy and safety of disease-modifying OA drugs, with the potential to act as diagnostic and prognostic tools. Currently, the diagnostic power of interleukin(IL)-6 and the relationship to disease burden of IL-1β, IL-15, tumor necrosis factor-α, and vascular endothelial growth factor make these the best candidates for assessment. Grouping appropriate cytokine markers together and assessing them collectively alongside other bone and cartilage degradation products will yield a more statistically powerful tool in research and clinical applications, and additionally aid in distinguishing between OA and a number of other diseases in which cytokines are known to have an involvement. Further large scale studies are needed to assess the validity and efficacy of current biomarkers, and to discover other potential biomarker candidates.展开更多
According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when c...According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.展开更多
AIM： To study the relationship between the polymorphisms in some cytokines and the outcome of hepatitis B virus （HBV） and hepatitis C virus （HCV） infection. METHODS： Samples were obtained from 203 patients infec...AIM： To study the relationship between the polymorphisms in some cytokines and the outcome of hepatitis B virus （HBV） and hepatitis C virus （HCV） infection. METHODS： Samples were obtained from 203 patients infected with HBV and/or HCV while donating plasma in 1987, and 74 controls were obtained from a rural area of North China. Antibodies to HBV or HCV antigens were detected by enzyme-linked imrnunoassay. The presence of viral particles in the serum was determined by nested reverse-transcriptase polymerase chain reaction （PCR）. Hepatocellular injury, as revealed by alanine aminotransferase （ALT） and aspartate aminotransferase level, was detected by a Beckman LX-20 analyzer. DNA was extracted from blood cells. Then, the single nucleotide polymorphisms of IL-2-330, IFN-γ＋874, IL-10-1082/-592 and IL-4-589 were investigated by restriction fragment length polymorphism-PCR or sequence specific primer-PCR.RESULTS： Persistent infection with HBV, HCV, and HBV/HCV coinfection was associated with IL-2-330 TT genotype and T allele, IFN-γ＋874 AA genotype, and IL-10-1082 AA genotype. The clinical outcome of HBV and/or HCV infection was associated with IL-2-330 TT genotype and T allele, IFN-γ＋874 AA genotype, and IL-10-1082 AA genotype. IL-2-330 GG genotype frequency showed a negative correlation with clinical progression, IL-10-1082 AA genotype frequency showed a positive correlation and IL-10-1082 AG genotype frequency showed a negative correlation with clinical progression. HCV RNA positive expression was associated with IL-10-1082 AA genotype and the A allele frequency. Abnormal serum ALT level was associated with IL-10-592 AC genotype frequency and IL-4-589 CC genotype, CT genotype, and the C allele. CONCLUSION： These results suggest that polymorphisms in some cytokine genes influence persistent HBV and HCV infection, clinical outcome, HCV replication, and liver damage.展开更多
BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further inf...BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.展开更多
Triptolide,a component of the Chinese herb Tripterygium wilfordii Hook F,has been proved to be effective in the treatment of rheumatoid arthritis(RA).However,its underlying mechanisms on RA have not yet been well esta...Triptolide,a component of the Chinese herb Tripterygium wilfordii Hook F,has been proved to be effective in the treatment of rheumatoid arthritis(RA).However,its underlying mechanisms on RA have not yet been well established.We observed the inhibitory effect of triptolide on the expression of inflammatory cytokines and proliferation of fibroblast-like synoviocytes(FLS)induced by the complex of interleukin-6(IL-6)and the soluble form of the IL-6 receptor(sIL-6R).Furthermore,to clarify the underlying mechanisms,we treated FLS with the Janus-activated kinase 2(JAK2)inhibitor/signal transducer and activator of transcription 3(STAT3)activation blocker AZD1480.In this study,immunohistochemical staining was used to identify vimentin(+)and CD68(−)in FLS.The FLS proliferation was measured by cell proliferation assay,and the cell cycles were analyzed by flow cytometry.Furthermore,ELISA was used to detect the expression of the inflammatory factors in culture solution.The expression levels of p-JAK2,JAK2,p-STAT3 and STAT3 were investigated through Western blotting analysis.The results showed that IL-6/sIL-6R significantly increased the cell proliferation and expression of inflammatory cytokines,including IL-6,interleukin-1β(IL-1β)and vascular endothelial growth factor(VEGF).Triptolide or AZD1480 inhibited the cell proliferation and inflammatory cytokine expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3.The study suggested that the physiological effects of triptolide on RA were due to its contribution to the inhibition of the inflammatory cytokine expression and FLS proliferation by suppressing the JAK2/STAT3 signaling pathway.It may provide an innovative insight into the effect of triptolide in preventing RA pathogenesis.展开更多
文摘BACKGROUND Multiple lines of evidence have indicated that pro-inflammatory cytokines play a role in the pathophysiology of gastric carcinoma(GC).AIM To identify potential serum cytokine-based biomarkers for GC diagnosis.METHODS The study cohort comprised 50 patients diagnosed with GC and 50 healthy control subjects.A panel of 7 pro-inflammatory cytokines,including interleukin(IL)-1β,IL-2,IL-6,IL-8,IL-12,tumor necrosis factor-α,and interferon-γ(IFN-γ)were quantified using multiplex Luminex assays.Comparative analyses were conducted to evaluate cytokine levels between the GC patients and healthy controls.The diagnostic potential of serum pro-inflammatory cytokines in differentiating GC patients from healthy individuals was assessed through receiver operating characteristic(ROC)curve analysis.The correlation between serum cytokine levels and disease severity,as classified by the tumor-node-metastasis staging system,was analyzed using Spearman's rank correlation coefficient.RESULTS In comparison to the control group,patients with GC demonstrated significantly elevated serum levels of IL-1β(t=-4.089,P<0.001),IL-6(t=-3.983,P<0.001),IL8(t=-5.460,P<0.001),and IFN-γ(t=-2.856,P=0.005).ROC curve analysis indicated that the area under the curve values for IL-1β,IL-6,and IL-8 exceeded 0.7,effectively distinguishing GC patients from healthy controls.Additionally,serum levels of IL-1β(r=0.424,P=0.012)and IL-6(r=0.742,P<0.001)were positively correlated with the T stage in GC patients.Similarly,serum concentrations of IL-1β(r=0.356,P=0.039)and IL-6(r=0.441,P=0.008)exhibited a positive association with the N stage in these patients.CONCLUSION These findings suggest that circulating pro-inflammatory cytokines,such as IL-1β,IL-6,and IL-8,may serve as potential biomarkers for the diagnosis of GC.
文摘This editorial critically analyses the recent article by Jung et al,which investigates the utility of 4-hour serum amylase and lipase as early blood markers for postendoscopic retrograde cholangiopancreatography(ERCP)acute pancreatitis prediction.Although these enzymes are valuable for the early diagnosis of post-ERCP pancreatitis,they lack specificity for disease etiology and provide limited insight into the molecular mechanisms underlying disease progression.Several cytokines,notably interleukin(IL)-6,tumor necrosis factor-alpha,and IL-8,are increased in post-ERCP pancreatitis and may serve as potential predictors for disease severity.The incorporation of these biomarkers in early enzymatic biomarkers and established prognostic scoring systems could further enhance their accuracy and allow for earlier,more effective management of patients with post-ERCP pancreatitis.
基金supported by the National Science and Technology Innovation 2030 Major Program(2021ZD0200900)National Key Research and Development Program of China(2022YFF0710901)+3 种基金National Natural Science Foundation of China(82021001,31825018)Biological Resources Program of the Chinese Academy of Sciences(KFJBRP-005)111 Project D18007a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘While viral infections can disturb the host gut microbiome,the dynamic alterations in microbial composition following infection remain poorly characterized.This study identified SRV-8-infected monkeys and classified them into five groups based on infection progression.16S rRNA amplicon sequencing revealed significant alterations in the relative and inferred absolute abundance of bacterial genera UCG-002,Agathobacter,Coprococcus,and Holdemanella during the early stage of SRV-8 infection,coinciding with provirus formation.These microbial shifts were accompanied by functional modifications in bacterial communities at the same stage.In contrast,ITS amplicon sequencing indicated no significant differences in fungal composition between healthy wild-type and SRV-8-infected monkeys.Spearman correlation analyses demonstrated close interactions between intestinal bacteria and fungi following SRV-8 infection.Additionally,SRV-8 seropositive groups exhibited significantly elevated mRNA expression levels of pro-inflammatory(TNF-α,IFN-γ,IL-1β,and IL-6)and anti-inflammatory(IL-10)cytokine genes,highlighting close associations between inflammatory cytokines and immune responses.Overall,these findings provide a comprehensive characterization of bacterial and fungal microbiota dynamics and inflammatory cytokine responses associated with SRV-8 infection,clarifying the pathobiological mechanisms underlying SRV-8 infection from the perspective of the gut microbiome.
文摘Anti-inflammatory activity ofRubus idaeus L. and possible mechanisms involved were explored in lipopolysaccharide （LPS）-treated RAW 264.7 cells. The effects of ethanol extract of R. idaeus on the levels of pro-inflammatory cytokines, including tumor necrosis factor-alfa （TNF-α）, interleukin-6 （IL-6） and interleukin-1 beta （IL-1β）, as well as pro-inflammatory mediators, such as nitric oxide （NO）, inducible nitric oxide synthase （iNOS） and cyclooxygenase-2 （COX-2） were studied by Sandwich ELISA, real-time PCR, and Western blot analysis. Moreover, the effects of ethanol extract of R. idaeus on anti-inflammatory cytokine interleukin-10 （IL-10） and anti-inflammatory mediator heme oxygenase-1 （HO-1） were also investigated using the same methods. Furthermore, nuclear factor-gB （NF-κB） level was assayed by immunocytochemistry. The results showed that the production of IL-1β, IL-6, NO, TNF-α and COX-2 in LPS-treated cells could be significantly inhibited （P〈0.01 or P〈0.05） by ethanol extract ofR. idaeus compared with that in the cells treated with LPS only. Meanwhile, the production of NF-r,B was also inhibited by the extract. Based on these results, the anti-inflammatory activity ofR. idaeus was attributed to the down-regulation of IL-6, IL-1β and TNF-α levels as well as gene expression of iNOS and COX-2 through the suppression of NF-κB activation, and induction of anti-inflammatory cytokine IL- 10 and anti-inflammatory mediator HO- 1.
基金supported by Regione Piemonte founding(RSF-4097-2009)
文摘Inflammatory events occurring in the distal part of an injured peripheral nerve have, nowadays, a great resonance. Investigating the timing of action of the several cytokines in the important stages of Wallerian degeneration helps to understand the regenerative process and design pharmacologic intervention that promotes and expedites recovery. The complex and synergistic action of inflammatory cytokines finally promotes axonal regeneration. Cytokines can be divided into pro- and anti-inflammatory cytokines that upregulate and downregulate, respectively, the production of inflammatory mediators. While pro-inflammatory cytokines are expressed in the first phase of Wallerian degeneration and promote the recruitment of macrophages, anti-inflammatory cytokines are expressed after this recruitment and downregulate the production of all cytokines, thus determining the end of the process. In this review, we describe the major inflammatory cytokines involved in Wallerian degeneration and the early phases of nerve regeneration. In particular, we focus on interleukin-1, interleukin-2, interleukin-6, tumor necrosis factor-β, interleukin-10 and transforming growth factor-β.
基金Supported by Huzhou Public Welfare Research Project Social Development Category,No.2021GYB09,No.2021GY38,No.2019GY26 and No.2019GZB02.
文摘BACKGROUND The pathogenesis of cognitive impairment in schizophrenia(SCZ)remains unclear.Accumulating studies showed that inflammatory-immune dysregulation and altered brain derived neurotrophic factor(BDNF)levels play a crucial role in the psychopathology of SCZ.However,their association with cognitive dysfunction in first-episode SCZ patients has not been thoroughly investigated.AIM To explore the interaction effects between cognitive function and inflammatory cytokines and BDNF in first-episode SCZ.METHODS The current study is a cross-sectional case-control investigation that recruited 84 patients with first-episode SCZ(SCZ group)and 80 healthy controls(HCs group)at the Huzhou Third Municipal Hospital between August 2021 and September 2023.ELISA was employed to measure the serum levels of interleukin(IL)-1β,IL-4,IL-6,IL-10,and BDNF.The Chinese brief cognitive test(C-BCT)and the positive and negative syndrome scales were measured the severity of cognitive impairment and psychiatric symptoms.RESULTS Compared to the HC group,the SCZ group exhibited elevated IL-1βand IL-6 levels,decreased BDNF levels,and reduced C-BCT scores(all P<0.001).In SCZ,BDNF was negatively correlated with IL-6(r=-0.324,P<0.05).Information processing speed was negatively correlated with IL-6(r=-0.315,P<0.05)and positively with BDNF(r=0.290,P<0.05);attention,working memory,comprehensive ability,and executive function were negatively correlated with IL-1βand IL-6(all P<0.05)and positively with BDNF(all P<0.05).Multiple regression analysis showed IL-6 influenced C-BCT dimensions(β=-0.218 to-0.327,all P<0.05);attention and executive ability were influenced by IL-1β(β=-0.199 to-0.261,all P<0.05);comprehensive executive ability was influenced by BDNF(β=0.209,P<0.05).CONCLUSION Our findings suggested that interrelationships between immune dysfunction and neurotrophic deficiency might underlie the pathological mechanisms of cognitive impairments in first-episode SCZ patients.
文摘Inflammatory bowel disease (IBD), which includes Crohn’s disease (CD) and ulcerative colitis (UC), rep- resents a group of chronic disorders characterized by inflammation of the gastrointestinal tract, typically with a relapsing and remitting clinical course. Mucosal mac- rophages play an important role in the mucosal im- mune system, and an increase in the number of newly recruited monocytes and activated macrophages has been noted in the inflamed gut of patients with IBD. Activated macrophages are thought to be major con- tributors to the production of inflammatory cytokines in the gut, and imbalance of cytokines is contributing to the pathogenesis of IBD. The intestinal inflammation in IBD is controlled by a complex interplay of innate and adaptive immune mechanisms. Cytokines play a key role in IBD that determine T cell differentiation of Th1, Th2, T regulatory and newly described Th17 cells. Cytokines levels in time and space orchestrate the development, recurrence and exacerbation of the inflammatory process in IBD. Therefore, several cyto- kine therapies have been developed and tested for the treatment of IBD patients.
文摘Nonalcoholic fatty liver disease (NAFLD) is a condition in which excess fat accumulates in the liver of a patient with no history of alcohol abuse or other causes for secondary hepatic steatosis. The pathogenesis of NAFLD and nonalcoholic steatohepatitis (NASH) has not been fully elucidated. The “two-hit“ hypothesis is probably a too simplified model to elaborate complex pathogenetic events occurring in patients with NASH. It should be better regarded as a multiple step process, with accumulation of liver fat being the first step, followed by the development of necroinflammation and fibrosis. Adipose tissue, which has emerged as an endocrine organ with a key role in energy homeostasis, is responsive to both central and peripheral metabolic signals and is itself capable of secreting a number of proteins. These adipocyte-specific or enriched proteins, termed adipokines, have been shown to have a variety of local, peripheral, and central effects. In the current review, we explore the role of adipocytokines and proinflammatory cytokines in the pathogenesis of NAFLD. We particularly focus on adiponectin, leptin and ghrelin, with a brief mention of resistin, visfatin and retinol-binding protein 4 among adipokines, and tumor necrosis factor-α, interleukin (IL)-6, IL-1, and briefly IL-18 among proinflammatory cytokines. We update their role in NAFLD, as elucidated in experimental models and clinical practice.
文摘AIM： To investigate the effect of short-chain fatty acids （SCFAs） on production of prostaglandin E2 （PGE2）, cytokines and chemokines in human monocytes. METHODS： Human neutrophils and monocytes were isolated from human whole blood by using 1-Step Polymorph and RosetteSep Human Monocyte Enrichment Cocktail, respectively. Human GPR41 and GPR43 mRNA expression was examined by quantitative realtime polymerase chain reaction, The calcium flux assay was used to examine the biological activities of SCFAs in human neutrophils and monocytes. The effect of SCFAs on human monocytes and peripheral blood mononuclear cells （PBMC） was studied by measuring PGE2, cytokines and chemokines in the supernatant. The effect of SCFAs in vivo was examined by intraplantar injection into rat paws. RESULTS： Human GPR43 is highly expressed in human neutrophils and monocytes. SCFAs induce robust calcium flux in human neutrophils, but not in human monocytes. In this study, we show that SCFAs can induce human monocyte release of PGE2 and that this effect can be enhanced in the presence of lipopolysaccharide （LPS）. In addition, we demonstrate that PGE2 production induced by SCFA was inhibited by pertussis toxin, suggesting the involvement of a receptor-mediated mechanism. Furthermore, SCFAs can specifically inhibit constitutive monocyte chemotactic protein-1 （MCP-1） production and LPS-induced interleukin-10 （IL-10） production in human monocytes without affecting the secretion of other cytokines and chemokines examined. Similar activities were observed in human PBMC for the release of PGE2, MCP-1 and IL-10 after 5CFA treatment. In addition, SCFAs inhibit LPS-induced production of tumor necrosis factor-α and interferon-7 in human PBIVlC. Finally, we show that SCFAs and LPS can induce PGE2 production in vivo by intraplantar injection into rat paws （P 〈 0.01）. CONCLUSION： SCFAs can have distinct antiinflammatory activities due to their regulation of PGE2, cytokine and chemokine release from human immune cells.
基金Supparted by the Ntiona1 Natura1 Science Foundation of China No.39670899.
文摘AIM:To observe the effect of acupuncture and moxibustion on the expression of IL-1beta and IL-6 mRNA in ulcerative colitis rats.METHODS:The SD rat ulcerative colitis model was created by immunological method associated with local stimulation. Colonic mucosa was prepared from human fresh surgical colonic specimens, homogenized by adding appropriate amount of normal saline and centrifuged at 3000r/min. The supernatant was collected for measurement of protein conentration and then mixed with Freund adjuvant. This antigen fluid was first injected into the plantae of the model group rats, and then into their plantae, dorsa, inguina and abdominal cavities (noFreund adjuvant for the last injection) again on the 10th, 17th, 24th and 31st day. When a certain titer of serum anti colonic antibody was reached, 2% formalin and antigen fluid (no Freund adjuvant) were administered separately by enema. The ulcerative colitis rat model was thus set up. The animals were randomly divided into four groups: model control group (MC, n = 8), electro acupuncture group (EA, n = 8), herbs partition moxibustion group (HPM 8), normal control group (NC,n = 8). HPM: Moxa cones made of refined mugwort floss were placed on the medicinal pad (medicinal pad dispensing: Radix Aconiti praeparata, cortex Cinnamomi, etc) for Qihai (RN 6) and Tianshu (ST 25, bilateral) and ignited. Two moxa cones were used for each acupoint once a day and 14 times in all. EA: Tianshu (bilateral) and Qihai were stimulated by the intermittent pulse with 2Hz frequency, 4mA intensity for 20 minutes once a day and 14 times in all. After treatment, rats of all four groups were killed simultaneously. The spleen was separated and the distal colon was dissected. Total tissue RNA was isolated by the guanidinium thiocyanate phenol chloroform extraction method. RT-PCR technique was used to study the expression of IL-1 beta and IL-6 mRNA.RESULTS:IL-1 beta and IL-6 mRNAs were not detected in the spleen and colonic mucosa of the NC rats, whereas they were significantly expressed in that of the MC rats.IL-1 beta and IL-6 mRNAs were markedly lower in the EA and HPM rats than that in MC rats. There was no significant difference between the levels of IL-1 beta and IL-6 mRNAs in the EA and HPM rats. The expressions of IL-1 beta and IL-6 mRNAs were nearly the same in the spleen and colon of all groups.CONCLUSION:Acupuncture and moxibustion greatly inhibited the expression of IL-1 beta and IL-6 mRNA in the experimental ulcerative colitis rats.
基金Supported by Grants from National Key Technologies R&D Program of 11th five-year plan, 2009ZX09501-015
文摘AIM： To investigate the correlation between the antifibrotic effect of baicalin and serum cytokine production in rat hepatic fibrosis, METHODS： Forty male Sprague-Dawley rats were divided randomly into four groups： normal control group, model group, baicalin-treated group, and colchicine-treated group. Except for the normal control group, all rats in the other groups were administered with carbon tetrachloride to induce hepatic fibrosis. At the same time, the last two groups were also treated with baicalin or colchicine. At the end of the 8 wk, all animals were sacrificed. Serum alanine aminotransferase （ALl＇）, aspartate aminotransferase （AST）, transforming growth factor （TGF）-β1, tumor necrosis factor （TNF）-α, interleukin （IL）-6 and IL-10 were measured. Liver index, hepatic hydroxyproline content and the degree of liver fibrosis were also evaluated. RESULTS： The levels of ALT, AST and liver index in the baicalin-treated group were markedly lower than those in the model group （ALT： 143.88 ± 14.55 U/L vs 193.58± 24.35 U/L; AST： 263.66 ± 44.23 U/L vs 404.37± 68.29 U/L; liver index： 0.033 ± 0.005 vs 0.049± 0.009, P 〈 0.01）. Baicalin therapy also significantly attenuated the degree of hepatic fibrosis, collagen area and collagen area percentage in liver tissue （P 〈 0.01）. Furthermore, the levels of serum TGF-β1, TNF-α and IL-6 were strikingly reduced in the baicalin-treated group compared with the model group, while the production of IL-10 was up-regulated： （TGF-β1：260.21 ± 31.01 pg/mL vs 375.49 ± 57.47 pg/mL; TNF-α： 193.40±15.18 pg/mL vs 260.04 ± 37.70 pg/mL; IL-α：339.87 ± 72.95 pg/mL vs 606.47 ± 130.73 pg/mL; IL-10：506.22 ± 112.07 pg/mL vs 316.95 ± 62.74 pg/mL, P 〈 0.01）. CONCLUSION： Baicalin shows certain therapeutic effects on hepatic fibrosis, probably by immunoregulating the imbalance between profibrotic and antifibrotic cytokines.
文摘AIM: To study the effect of cholecystokinin-octapeptide (CCK-8) on systemic hypotension and cytokine production in lipopolysaccharide (LPS)-induced endotoxic shock (ES) rats. METHODS: The changes of blood pressure were observed using physiological record instrument in four groups of rats: LPS (8mg.kg(-1),iv) induced ES; CCK-8 (40 microg.kg(-1), iv) pretreatment 10 min before LPS (8mg.kg(-1)); CCK-8 (40 micro.kg(-1), iv) or normal saline (control) groups. Differences in tissue and circulating specificity of the proinflammatory cytokines (TNF-alpha, IL-1beta and IL-6) were assayed with ELISA kits. RESULTS: CCK-8 reversed LPS-induced decrease of mean artery blood pressure (MABP) in rats. Compared with control, LPS elevated the serum level of IL-6 significantly (3567 +/- 687 ng.L(-1) vs 128 +/- 22 ng.L(-1), P【0.01), while contents of TNF-alpha and IL-1beta elevated significantly (277 +/- 86 ng.L(-1) vs not detectable and 43 +/- 9 ng.L(-1) vsnot detectable, P【0.01) but less extent than IL-6. CCK-8 significantly inhibited the LPS-induced increase in serum TNF-alpha IL-1beta and IL-6. LPS elevated spleen and lung content of IL-1beta significantly (5184 +/- 85 ng.L(-1) vs 1047 +/- 21 ng.L(-1) and 4050 +/- 614 ng.L(-1) vs not detectable, P【0.01), while levels of TNF-alpha and IL-6 also rose significantly but in less extent than IL-1beta. CCK-8 inhibited the LPS-induced increase of the cytokines in spleen and lung. In the heart, CCK-8 significantly inhibited LPS-induced increase of TNF-alpha (864 +/- 123 ng.L(-1) in CCK-8+LPS group vs 1599 +/- 227 ng.L(-1) in LPS group, P 【 0.01), and IL-1beta (282 +/- 93 ng.L(-1) in CCK-8+LPS group vs 621 +/- 145ng.L(-1) in LPS group, P 【 0.01). CONCLUSION: CCK-8 reverses ES, which may be related to its inhibitory effect on the overproduction of cytokines.
文摘Abstract AIM To investigate whether PMN from patients with IBD or infectious colitis, respectively, secrete increased amounts of pro inflammatory cytokines and can be regulated by IL 10. METHODS Secretion (ELISA) as well as corresponding mRNA levels (semiquantitative RT PCR) of pro inflammatory cytokines (IL 1β, TNF α) and of IL 1 receptor antagonist were assessed in peripheral PMN. RESULTS PMN from patients with IBD are primed to secrete enhanced amounts of pro inflammatory cytokines accompanied by detection of corresponding mRNAs in comparison with normal controls. This finding is not specific for IBD but rather reflects intestinal inflammation in general. IL 10 markedly inhibited proinflammatory cytokine secretion as well as corresponding mRNA concentrations. CONCLUSION PMN are an important source of pro inflammatory cytokines in patients with intestinal inflammation and can be downregulated by IL 10.
文摘AIM: To investigate the biliary biochemical constituents and cytokines in infantile hepatitis syndrome (IHS). METHODS: From 42 IHS subjects and 21 controls, serum and biliary biochemical constituents, including total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GT), total bile acid (TBA), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) both in bile and serum, were assayed. The subjects with IHS were divided into a cholestasis group (n = 21) and a hepatitis group (n = 21). RESULTS: In the cholestasis group, serum TBIL, DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01); and also the biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control, whereas biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the cholestasis group, serum IL-6 and TNF-α levels were lower than those in bile (P < 0.01). In the hepatitis group, serum DBIL, ALT, γ-GT, TBA, IL-6 and TNF-α levels were higher than those in the control (P < 0.01 or 140.57 ± 70.32 vs 79.06 ± 35.25, P < 0.05), while biliary TBIL, DBIL, γ-GT and TBA levels were lower than those in the control (P < 0.01), and biliary IL-6 and TNF-α levels were higher than those in the control (P < 0.01). In the hepatitis group, serum IL-6 and TNF-α levels were also lower than those in bile (P < 0.01). Serum TBIL, DBIL, γ-GT, IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitis group, while biliary IL-6 and TNF-α levels in the cholestasis group were higher than those in the hepatitisgroup. Biliary IL-6 and TNF-α were found to be more significantly increased than serum IL-6 and TNF-α in IHS (P < 0.01). The biliary IL-6 and TNF-α levels were positively correlated with serum DBIL, TBA and γ-GT levels in IHS subjects. CONCLUSION: Biliary biochemical constituents alter in coincidence with pathological changes in hepatocellular injury. Cholestasis is more serious in IHS patients of cholestasis subtype. Assay of biliary IL-6 and TNF-α levels can be specific and sensitive to determine the inflammatory status of impaired liver in IHS.
文摘Gene therapy offers a new approach for treatment of cancer. Transfer of genes encoding immunostimulatory cytokines has been used with remarkable success to eliminate cancer in animals. However, clinical trials in patients with this strategy had limited efficacy. Therefore, improvement ofgene transfer vector system is necessary. A hybrid viral vector, consisting of SFV replicon with either murine IL-12 or reporter LacZ gene, was constructed. This hybrid vector showed specificity and high level of expression in HCC both in vitro and in vivo. In a rat orthotropic liver tumor model, treatment of established tumors by the hybrid vector with raiL- 12 gene resulted in a strong anti-tumor activity without accompanying toxicity. Subsequently, a helper-dependent adenovirus vectors containing a mifepristone （RU486） inducible system was constructed for controlled and liver-specific expression of human interleukin 12 （hIL- 12） （HD-Ad/RUhIL- 12） and mouse IL-12 （mIL-12） （HD-Ad/RUmIL-12）. Data showed that high and sustained serum levels of hlL-12 could be attained by continuing administration of RU486 every 12 or 24 h. Repetitive induction ofhlL-12 could be obtained over, at least, a period of 48 weeks after a single injection of HD-Ad/RUhlL-12. Treatment of liver metastases with of HD-Ad/RUmIL- 12 plus RU846 resulted in complete tumor regression in all animals. Then, different cytokine genes were inserted into conditional replicative adenoviruses vectors （also called oncolytic adenovirus）. Replication ofadenovirus in tumor cells would kill tumor cells and release viruses, which infect surrounding tumor cells. The combination of cytopathic effect by oncolytic adenovirus and biological effect of transgene would exert strong antitumor activity. These new types of vectors may provide a potent and safe tool for cancer gene therapy.
基金Supported by Ratchadapiseksompotch Fund(RA55/22)Faculty of Medicine,Chulalongkorn University and Office of the Higher Education Commission(CU-NRU,Aging Society Cluster)
文摘Osteoarthritis(OA) is a debilitating degenerative joint disease particularly affecting weightbearing joints within the body, principally the hips and knees. Current radiographic techniques are insufficient to show biochemical changes within joint tissue which can occur many years before symptoms become apparent. The need for better diagnostic and prognostic tools is heightened with the prevalence of OA set to increase in aging and obese populations. As inflammation is increasingly beingconsidered an important part of OAs pathophysiology, cytokines are being assessed as possible candidates for biochemical markers. Cytokines, both pro- and antiinflammatory, as well as angiogenic and chemotactic, have in recent years been studied for relevant characteristics. Biochemical markers show promise in determination of the severity of disease in addition to monitoring of the efficacy and safety of disease-modifying OA drugs, with the potential to act as diagnostic and prognostic tools. Currently, the diagnostic power of interleukin(IL)-6 and the relationship to disease burden of IL-1β, IL-15, tumor necrosis factor-α, and vascular endothelial growth factor make these the best candidates for assessment. Grouping appropriate cytokine markers together and assessing them collectively alongside other bone and cartilage degradation products will yield a more statistically powerful tool in research and clinical applications, and additionally aid in distinguishing between OA and a number of other diseases in which cytokines are known to have an involvement. Further large scale studies are needed to assess the validity and efficacy of current biomarkers, and to discover other potential biomarker candidates.
文摘According to the minimal criteria of the International Society of Cellular Therapy, mesenchymal stem cells(MSCs) are a population of undifferentiated cells defined by their ability to adhere to plastic surfaces when cultured under standard conditions, express a certain panel of phenotypic markers and can differentiate into osteogenic, chondrogenic and adipogenic lineages when cultured in specific inducing media. In parallel with their major role as undifferentiated cell reserves, MSCs have immunomodulatory functions which are exerted by direct cell-to-cell contacts, secretion of cytokines and/or by a combination of both mechanisms. There are no convincing data about a principal difference in the profile of cytokines secreted by MSCs isolated from different tissue sources, although some papers report some quantitative but not qualitative differences in cytokine secretion. The present review focuses on the basic cytokines secreted by MSCs as described in the literature by which the MSCs exert immunodulatory effects. It should be pointed out that MSCs themselves are objects of cytokine regulation. Hypothetical mechanisms by which the MSCs exert their immunoregulatory effects are also discussed in this review. These mechanisms may either influence the target immune cells directly or indirectly by affecting the activities of predominantly dendritic cells. Chemokines are also discussed as participants in this process by recruiting cells of the immune systems and thus making them targets of immunosuppression. This review aims to present and discuss the published data and the personal experience of the authors regarding cytokines secreted by MSCs and their effects on the cells of the immune system.
文摘AIM： To study the relationship between the polymorphisms in some cytokines and the outcome of hepatitis B virus （HBV） and hepatitis C virus （HCV） infection. METHODS： Samples were obtained from 203 patients infected with HBV and/or HCV while donating plasma in 1987, and 74 controls were obtained from a rural area of North China. Antibodies to HBV or HCV antigens were detected by enzyme-linked imrnunoassay. The presence of viral particles in the serum was determined by nested reverse-transcriptase polymerase chain reaction （PCR）. Hepatocellular injury, as revealed by alanine aminotransferase （ALT） and aspartate aminotransferase level, was detected by a Beckman LX-20 analyzer. DNA was extracted from blood cells. Then, the single nucleotide polymorphisms of IL-2-330, IFN-γ＋874, IL-10-1082/-592 and IL-4-589 were investigated by restriction fragment length polymorphism-PCR or sequence specific primer-PCR.RESULTS： Persistent infection with HBV, HCV, and HBV/HCV coinfection was associated with IL-2-330 TT genotype and T allele, IFN-γ＋874 AA genotype, and IL-10-1082 AA genotype. The clinical outcome of HBV and/or HCV infection was associated with IL-2-330 TT genotype and T allele, IFN-γ＋874 AA genotype, and IL-10-1082 AA genotype. IL-2-330 GG genotype frequency showed a negative correlation with clinical progression, IL-10-1082 AA genotype frequency showed a positive correlation and IL-10-1082 AG genotype frequency showed a negative correlation with clinical progression. HCV RNA positive expression was associated with IL-10-1082 AA genotype and the A allele frequency. Abnormal serum ALT level was associated with IL-10-592 AC genotype frequency and IL-4-589 CC genotype, CT genotype, and the C allele. CONCLUSION： These results suggest that polymorphisms in some cytokine genes influence persistent HBV and HCV infection, clinical outcome, HCV replication, and liver damage.
基金Supported by the Medical University of Sofia,No.22.2012-2013Trakia University of Stara Zagora,No.1.2016 and No.2.2017.
文摘BACKGROUND The connection between inflammatory bowel disease(IBD)and colorectal cancer(CRC)is well-established,as persistent intestinal inflammation plays a substantial role in both disorders.Cytokines may further influence the inflammation and the carcinogenesis process.AIM To compare cytokine patterns of active IBD patients with early and advanced CRC.METHODS Choosing a panel of cytokines crucial for Th17/Treg differentiation and behavior,in colon specimens,as mRNA biomarkers,and their serum protein levels.RESULTS We found a significant difference between higher gene expression of FoxP3,TGFb1,IL-10,and IL-23,and approximately equal level of IL-6 in CRC patients in comparison with IBD patients.After stratification of CRC patients,we found a significant difference in FoxP3,IL-10,IL-23,and IL-17A mRNA in early cases compared to IBD,and IL-23 alone in advanced CRC.The protein levels of the cytokines were significantly higher in CRC patients compared to IBD patients.CONCLUSION Our findings showed that IL-6 upregulation is essential for both IBD and CRC development until the upregulation of other Th17/Treg related genes(TGFb1,IL-10,IL-23,and transcription factor FoxP3)is a crucial primarily for CRC development.The significantly upregulated IL-6 could be a potential drug target for IBD and prevention of CRC development as well.
基金the Shenzhen City Science and Technology Bureau of China(No.JCYJ20170307111755218)“San-Ming”Project of Medicine in Shenzhen(No.SZSM201612092).
文摘Triptolide,a component of the Chinese herb Tripterygium wilfordii Hook F,has been proved to be effective in the treatment of rheumatoid arthritis(RA).However,its underlying mechanisms on RA have not yet been well established.We observed the inhibitory effect of triptolide on the expression of inflammatory cytokines and proliferation of fibroblast-like synoviocytes(FLS)induced by the complex of interleukin-6(IL-6)and the soluble form of the IL-6 receptor(sIL-6R).Furthermore,to clarify the underlying mechanisms,we treated FLS with the Janus-activated kinase 2(JAK2)inhibitor/signal transducer and activator of transcription 3(STAT3)activation blocker AZD1480.In this study,immunohistochemical staining was used to identify vimentin(+)and CD68(−)in FLS.The FLS proliferation was measured by cell proliferation assay,and the cell cycles were analyzed by flow cytometry.Furthermore,ELISA was used to detect the expression of the inflammatory factors in culture solution.The expression levels of p-JAK2,JAK2,p-STAT3 and STAT3 were investigated through Western blotting analysis.The results showed that IL-6/sIL-6R significantly increased the cell proliferation and expression of inflammatory cytokines,including IL-6,interleukin-1β(IL-1β)and vascular endothelial growth factor(VEGF).Triptolide or AZD1480 inhibited the cell proliferation and inflammatory cytokine expression in IL-6/sIL-6R-stimulated FLS by suppressing JAK2/STAT3.The study suggested that the physiological effects of triptolide on RA were due to its contribution to the inhibition of the inflammatory cytokine expression and FLS proliferation by suppressing the JAK2/STAT3 signaling pathway.It may provide an innovative insight into the effect of triptolide in preventing RA pathogenesis.
