摘要
目的 探讨抗白介素 12 (IL 12 )单克隆抗体治疗实验性慢性结肠炎的机制。方法 用严重联合免疫缺陷 (SCID)小鼠 ,植入同基因源性CD4 5RBhighCD+4 T细胞 ,诱导慢性结肠炎 ,并进行抗IL 12单克隆抗体治疗和观察IL 12在慢性结肠炎中的病理生理作用。结果 在T细胞植入 4周后结肠组织内IL 12P4 0 mRNA含量明显升高 ,抗IL 12单克隆抗体有效地阻断了慢性结肠炎的发生 ,降低了结肠粘膜内CD4 +T细胞和巨噬细胞浸润 ,并抑制肠粘膜内固有层CD4 +T细胞分泌IL 2和IFN γ。结论 IL 12参与了慢性实验性结肠炎的病理生理过程 ,阻断IL
Aim To explore the mechanism of antiinterlukin 12 monoclonal antibody in blocking the development of chronic colitis in SCID mice.Methods An adoptive transfer model of chronic colitis in severe combined immune deficient (SCID) mice was set up by reconstitution with syngeneic CD 45 RB high CD + 4T cells.These mice were treated with anti IL 12 mAb to investigate the in vivo relevance of IL 12 to the pathogenesis.Results IL 12 p40 mRNA in inflamed colon was induced shortly after T cell transfer and maintained at a stable level after weeks 4. Administration of anti IL 12 on days 0,14,and 28 after T cell transfer effectively prevented wasting disease with severe colitis in SCID recipients.Anti IL 12 treatment abrogated mucosal inflammation with significantly diminished leukocyte infiltration (CD 4 cells,F4/80 macrophages) and down regulation of proinflammatory cytokines (i.e., interferon γ and IL 2).Conclusions These findings indicate that IL 12 is essential for the induction of experimental colitis through effects on proinflammatory cytokine production and on leukocyte infiltration in the colon.Target treatment against IL 12 may have therapeutic potential in Crohn's disease. [
出处
《胃肠病学和肝病学杂志》
CAS
2001年第2期131-136,共6页
Chinese Journal of Gastroenterology and Hepatology
