Brennan Fionula, Beech Jonathan
Kennedy Institute of Rheumatology Division, Imperial College London, London, UK.
Curr Opin Rheumatol. 2007 May;19(3):296-301. doi: 10.1097/BOR.0b013e32805e87f1.
There have recently been fewer publications describing novel cytokines in rheumatoid arthritis. In the present review we focus on cytokines not previously implicated in contributing to the pathogenesis of rheumatoid arthritis.
The detection of IL-17 and factors that drive the differentiation and expansion of ThIL-17 cells, particularly in mouse models, clearly place IL-17 as a potential therapeutic target in rheumatoid arthritis. The emergence of other novel cytokines, notably IL-20 and IL-22, is of interest, not least by displaying proinflammatory effects particularly on fibroblasts - in contrast to their family member IL-10, the most potent anti-inflammatory cytokine. IL-32 is also of interest, with proinflammatory effects both on myeloid and nonmyeloid cells.
It is unclear whether the novel cytokines described in the present review will influence clinical practise. The involvement of IL-17 in murine arthritis may not translate as effectively to human arthritis - the ultimate test is a clinical trial in humans. The lack of efficacy of a recent anti-MCP-1/CCL-2 trial in rheumatoid arthritis highlights this dilemma. Finally, while technological advances including microarray analysis have broadened the scope for cytokine detection in rheumatoid arthritis, these methods have yet to translate to therapy in the clinic.
近期描述类风湿关节炎中新细胞因子的出版物较少。在本综述中,我们聚焦于此前未被认为与类风湿关节炎发病机制相关的细胞因子。
白细胞介素-17(IL-17)以及驱动Th17细胞分化和扩增的因子的发现,尤其是在小鼠模型中的发现,明确将IL-17列为类风湿关节炎潜在的治疗靶点。其他新细胞因子的出现,特别是IL-20和IL-22,值得关注,尤其是它们表现出促炎作用,特别是对成纤维细胞的作用——这与它们家族中最有效的抗炎细胞因子IL-10形成对比。IL-32也值得关注,它对髓样细胞和非髓样细胞都有促炎作用。
目前尚不清楚本综述中描述的新细胞因子是否会影响临床实践。IL-17在小鼠关节炎中的作用可能无法有效地转化到人类关节炎中——最终的检验是在人体中进行临床试验。近期一项抗单核细胞趋化蛋白-1/CCL-2试验在类风湿关节炎中缺乏疗效凸显了这一困境。最后,虽然包括微阵列分析在内的技术进步拓宽了类风湿关节炎中细胞因子检测的范围,但这些方法尚未转化为临床治疗手段。