Interleukin 6 plays a key role in the development of antigen-induced arthritis
Interleukin 6 plays a key role in the development of antigen-induced arthritis
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DOI：
10.1073/pnas.95.14.8222
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发表时间：
1998-07-07
影响因子：
11.1
通讯作者：
Kishimoto, T
中科院分区：
文献类型：
--
作者：
Ohshima, S;Saeki, Y;Kishimoto, T
为了研究白细胞介素（IL）-6在类风湿性关节炎（RA）发生中的直接作用，将IL-6缺陷（IL-6 -/-）小鼠与具有抗原诱导关节炎（AIA）易感性遗传背景的C57 BL/6小鼠回交8代。在诱导AIA后，在IL-6-缺陷（IL-6 -/-）小鼠和野生型（IL-6 +/+）同窝小鼠之间进行组织学和免疫学比较。尽管所有IL-6 +/+小鼠都发生了严重的关节炎，但在IL-6 -/-小鼠中仅观察到轻度关节炎。番红O染色显示IL-6 -/-小鼠的关节软骨保存良好，而IL-6 +/+小鼠的关节软骨被完全破坏。此外，在IL-6 -/-小鼠的发炎关节中检测到IL-1 β和肿瘤坏死因子α的mRNA表达相当，但未检测到IL-6的mRNA表达，这表明IL-6可能在软骨破坏中比IL-1 β或肿瘤坏死因子α发挥更关键的作用。在IL-6 -/-小鼠中引发了淋巴结细胞中的抗原特异性体外增殖反应和体内抗体产生，但它们减少到不到IL-6 +/+小鼠中发现的一半。IL-6 -/-小鼠的淋巴结细胞在体外培养中产生的Th 2细胞因子比IL 6 +/+小鼠在抗原特异性或非特异性刺激下产生的Th 2细胞因子多得多。综上所述，这些结果表明，IL-6可能在AIA的诱导期和效应期的发展中发挥关键作用，并且IL-6的阻断可能有益于类风湿性关节炎的治疗。
To investigate the direct role of interleukin (IL)-6 in the development of rheumatoid arthritis, IL-6-deficient (IL-6 -/-) mice were backcrossed for eight gener ations into C57BL/6 mice, a strain of mice with a genetic background of susceptibility for antigen-induced arthritis (AIA). Both histological and immunological comparisons were made between IL-6-deficient (IL-6 -/-) mice and wild-type (IL-6 +/+) littermates after the induction of AIA, Although all IL-6 +/+ mice developed severe arthritis, only mild arthritis was observed in IL-6 -/- mice. Safranin O staining demonstrated that articular cartilage was well preserved in IL-6 -/- mice, whereas it was destroyed completely in IL-6 +/+ mice. In addition, comparable mRNA expression for both IL-1 beta and tumor necrosis factor alpha, but not for IL-6, was detected in the inflamed joints of IL-6 -/- mice, suggesting that IL-6 may play a more crucial role in cartilage destruction than either IL-1 beta or tumor necrosis factor alpha, In immunological comparisons, both antigen-specific in vitro proliferative response in lymph node cells and in vivo antibody production were elicited in IL-6 -/- mice, but they were reduced to less than half of that found in IL-6 +/+ mice. Lymph node cells of IL-6 -/- mice produced many more Th2 cytokines than did IL 6 +/+ mice with either antigen-specific or nonspecific stimulation in in vitro culture. Taken together, these results indicate that IL-6 may play a key role in the development of AIA at the inductive as well as the effector phase, and the blockade of IL-6 is possibly beneficial in the treatment of rheumatoid arthritis.