Issekutz A C, Meager A, Otterness I, Issekutz T B
Department of Paediatrics, Dalhousie University, Halifax, NS, Canada.
Clin Exp Immunol. 1994 Jul;97(1):26-32. doi: 10.1111/j.1365-2249.1994.tb06574.x.
The mediators involved in leucocyte recruitment to joints during arthritis are not fully defined, but two important proinflammatory cytokines, IL-1 and tumour necrosis factor-alpha (TNF-alpha), are produced in joints in rheumatoid arthritis (RA). We investigated in the rat adjuvant arthritis model whether endogenous IL-1 and TNF-alpha contribute to joint inflammation and polymorphonuclear leucocyte (PMNL) and T lymphocyte infiltration. The migration of 51Cr-labelled rat blood PMNL and 111In-labelled T lymphocytes to the joints of rats with adjuvant arthritis was measured along with plasma protein extravasation, which was quantified using 125I-labelled human albumin. Rats with active arthritis of 5 days' duration received i.p. non-immune serum, polyclonal neutralizing anti-serum to rat TNF-alpha, antiserum to IL-1 alpha and IL-1 beta, or both anti-TNF plus anti-IL-1 for 5 days. Treatment with anti-IL-1 alpha and IL-1 beta did not affect plasma protein extravasation, or PMNL or T lymphocyte accumulation in the joints (i.e. talar joint, hind paws, and tail) despite the fact that this treatment inhibited 80-90% of the PMNL migration into dermal sites injected with IL-1 alpha or IL-1 beta. In contrast, anti-TNF-alpha treatment significantly improved clinical scores, decreased plasma protein extravasation by 60-80%, inhibited PMNL accumulation by 40-50% and decreased T lymphocyte accumulation by 30-50%. Treatment with anti-IL-1, together with anti-TNF-alpha, significantly potentiated the inhibition of T lymphocyte accumulation observed with anti-TNF-alpha alone. These results indicate that endogenous TNF-alpha production may play an important role in the inflammatory changes and leucocyte recruitment in this experimental model of human arthritis, while IL-1 may have a less important role in leucocyte recruitment to these joints.
关节炎期间白细胞募集至关节所涉及的介质尚未完全明确，但类风湿关节炎（RA）患者关节中会产生两种重要的促炎细胞因子，即白细胞介素 -1（IL -1）和肿瘤坏死因子 -α（TNF -α）。我们在大鼠佐剂性关节炎模型中研究内源性IL -1和TNF -α是否会导致关节炎症以及多形核白细胞（PMNL）和T淋巴细胞浸润。我们测量了51Cr标记的大鼠血液PMNL和111In标记的T淋巴细胞向佐剂性关节炎大鼠关节的迁移情况，同时还测量了血浆蛋白外渗情况，血浆蛋白外渗通过125I标记的人白蛋白进行定量。病程为5天的活动性关节炎大鼠腹腔注射非免疫血清、抗大鼠TNF -α多克隆中和抗血清、抗IL -1α和IL -1β抗血清或抗TNF加抗IL -1，持续5天。尽管抗IL -1α和IL -1β治疗能抑制80 - 90%的PMNL迁移至注射IL -1α或IL -1β的皮肤部位，但该治疗对血浆蛋白外渗、关节（即距骨关节、后爪和尾巴）中的PMNL或T淋巴细胞积聚没有影响。相比之下，抗TNF -α治疗显著改善了临床评分，使血浆蛋白外渗降低了60 - 80%，抑制PMNL积聚40 - 50%，并使T淋巴细胞积聚减少30 - 50%。抗IL -1与抗TNF -α联合治疗显著增强了单独使用抗TNF -α时对T淋巴细胞积聚的抑制作用。这些结果表明，在该人类关节炎实验模型中，内源性TNF -α的产生可能在炎症变化和白细胞募集中起重要作用，而IL -1在这些关节的白细胞募集中可能作用较小。
