Walmsley M, Butler D M, Marinova-Mutafchieva L, Feldmann M
Kennedy Institute of Rheumatology, London, UK.
Immunology. 1998 Sep;95(1):31-7. doi: 10.1046/j.1365-2567.1998.00568.x.
Interleukin-11 (IL-11) is a cytokine belonging to the IL-6 family which has both pro- and anti-inflammatory potential. Like IL-6 it can diminish tumour necrosis factor-alpha and IL-1 production, and augment immunoglobulin synthesis. We have explored the immunomodulatory effects of IL-11 treatment in mice in a model of inflammatory autoimmune joint disease, collagen-induced arthritis (CIA). Recombinant human IL-11 was administered at various doses to DBA/1 mice after the onset of CIA. IL-11 treatment caused a significant reduction in the clinical severity of established CIA, which was associated with protection from joint damage, as assessed by histology. Although there was a suggestion at high doses of IL-11 that the anticollagen type II (CII) response may have been augmented, there was no statistically significant effect of IL-11 treatment on anti-CII antibody levels. Similarly, the acute-phase reactant serum amyloid P was only elevated in mice receiving very high doses (50-100 microgram/day) of IL-11. Endogenous IL-11 was abundantly produced in synovial membrane cultures derived from CII-immunized mice with active disease, suggesting that, as in rheumatoid arthritis, this cytokine is spontaneously produced in the inflammatory response in CIA. The results presented here demonstrate an anti-arthritic immunoregulatory role for IL-11 in murine CIA, and suggest that IL-11 is a candidate therapeutic molecule for human inflammatory arthritic diseases.
白细胞介素-11（IL-11）是一种属于IL-6家族的细胞因子，具有促炎和抗炎的双重潜力。与IL-6一样，它可以减少肿瘤坏死因子-α和IL-1的产生，并增强免疫球蛋白的合成。我们在炎症性自身免疫性关节疾病——胶原诱导性关节炎（CIA）模型中，研究了IL-11治疗对小鼠的免疫调节作用。在CIA发病后，将重组人IL-11以不同剂量给予DBA/1小鼠。IL-11治疗使已建立的CIA的临床严重程度显著降低，组织学评估显示这与关节损伤的保护有关。尽管高剂量的IL-11提示抗II型胶原（CII）反应可能增强，但IL-11治疗对抗CII抗体水平没有统计学上的显著影响。同样，急性期反应物血清淀粉样蛋白P仅在接受非常高剂量（50 - 100微克/天）IL-11的小鼠中升高。内源性IL-11在来自患有活动性疾病的CII免疫小鼠的滑膜培养物中大量产生，这表明，与类风湿性关节炎一样，这种细胞因子在CIA的炎症反应中是自发产生的。此处呈现的结果证明了IL-11在小鼠CIA中具有抗关节炎的免疫调节作用，并表明IL-11是人类炎症性关节炎疾病的候选治疗分子。
