国产白细胞介素-1受体阻滞剂对胶原性关节炎大鼠淋巴细胞及巨噬细胞功能的影响

Effects of interleukin-1 receptor antagonist on lymphocyte and macrophage of rats with collagen-induced arthritis

目的:观察国产白细胞介素-1受体阻滞剂(IL-1ra)对大鼠胶原性关节炎(CIA)的影响。方法:鸡Ⅱ型胶原诱导大鼠CIA模型,关节评分法观察关节炎的发生情况;~3H-TdR掺入法检测T细胞、B细胞增殖反应;采用小鼠淋巴细胞增殖法检测IL-1活性;放免法检测大鼠腹腔巨噬细胞(PMφ)培养上清液肿瘤坏死因子(TNF)和前列腺素E_2(PGE_2)的含量。结果:CIA大鼠在致炎后d10,出现关节红肿,刀豆蛋白(ConA)或脂多糖(LPS)诱导的T和B淋巴细胞增殖反应增强;PMφ产生IL-1,TNF-α,PGE_2的水平升高。IL-1ra(7.5,30,120mg·kg^(-1)·d^(-1))和阳性对照组(anakinra 120mg·kg^(-1)·d^(-1))sc,连续7d,均能减轻CIA大鼠关节局部炎症,降低关节评分;IL-1ra(30,120mg·kg^(-1)·d^(-1))能明显降低CIA大鼠过高的T淋巴细胞增殖反应,IL-1ra(7.5,30,120mg·kg^(-1)·d^(-1))能明显降低CIA大鼠B淋巴细胞增殖反应;降低CIA大鼠PMφ产生过高的IL-1,TNF-α及PGE_2水平。结论:IL-1ra对CIA大鼠淋巴细胞和巨噬细胞的增殖反应具有抑制作用。

Objective:To investigate protections of interleukin-1 receptor antagonist (IL-lra) against collagen-induced arthritis (CIA) in rats. Methods: A CIA model was set up in SD rats by subcutaneous injection with type II collagen. The severity of arthritis was rated with arthritis scores. The examination of conA-and lipid polysaccharide (LPS)-induced splenocytes proliferation and interleukin-1 (IL-1) activities were conducted using a 3H-TdR intake method. Tumor necrosis factor alpha (TNF-α) and PGE_2 in the culture broth of macrophage (PMΦ) were quantified using radioimmunoassay. Results: The conA or LPS increased the level of T-and B-lymphocyte in 10 days after CIA in rats. The local inflammatory symptoms and B lymphocytes proliferation were reduced after subcutaneous injection with IL-lra at 7.5,30 and 120mg·kg^(-1)·d for 7 days, and T lymphocyte proliferation was suppressed when IL-lra at 30 and 120mg·kg^(-1)·d^(-1) was s. c. given in rats with CIA. The IL-1, TNF-α and PGR_2 levels in the PMΦ were inhibited by IL-1ra. Conclusion: IL-1ra inhibits the proliferation of lymphocytes and macrophage in the CIA rats.