Kim Eugene Y, Moudgil Kamal D
Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Immunol Lett. 2008 Oct 30;120(1-2):1-5. doi: 10.1016/j.imlet.2008.07.008. Epub 2008 Aug 9.
The pro-inflammatory cytokines play a critical role in the initiation and propagation of autoimmune arthritis and many other disorders resulting from a dysregulated self-directed immune response. These cytokines influence the interplay among the cellular, immunological and biochemical mediators of inflammation at multiple levels. Regulation of the pro-inflammatory activity of these cytokines is generally perceived to be mediated by the anti-inflammatory and immunosuppressive cytokines such as IL-4, IL-10, or TGF-beta. However, increasing evidence is accumulating in support of the regulatory attributes of the pro-inflammatory cytokines themselves, in studies conducted in animal models of diabetes, multiple sclerosis, uveitis, and lupus. The results of our recent studies have shown that the pro-inflammatory cytokines, TNF-alpha and IFN-gamma, can suppress arthritic inflammation in rats, and also contribute to resistance against arthritis. These results are of paramount significance not only in fully understanding the pathogenesis of autoimmune arthritis, but also in anticipating the full ramifications of the in vivo neutralization of the pro-inflammatory cytokines, including that for therapeutic purposes.
促炎细胞因子在自身免疫性关节炎以及许多其他由自我导向免疫反应失调导致的疾病的起始和传播中起着关键作用。这些细胞因子在多个层面影响炎症的细胞、免疫和生化介质之间的相互作用。这些促炎细胞因子的促炎活性调节通常被认为是由抗炎和免疫抑制细胞因子如白细胞介素-4、白细胞介素-10或转化生长因子-β介导的。然而，在糖尿病、多发性硬化症、葡萄膜炎和狼疮的动物模型研究中，越来越多的证据支持促炎细胞因子本身的调节特性。我们最近的研究结果表明，促炎细胞因子肿瘤坏死因子-α和干扰素-γ可以抑制大鼠的关节炎炎症，并且还有助于抵抗关节炎。这些结果不仅对于全面理解自身免疫性关节炎的发病机制至关重要，而且对于预测促炎细胞因子体内中和的全部影响（包括用于治疗目的的影响）也至关重要。
