Zhou Xiaoxia, Schmidtke Peter, Zepp Fred, Meyer Claudius U
Paediatric Immunology & Infectious Diseases, University Hospital Mainz, Obere Zahlbacher Str. 63, D-55131 Mainz, Germany.
Curr Drug Targets Immune Endocr Metabol Disord. 2005 Dec;5(4):465-75. doi: 10.2174/156800805774912926.
More than forty cytokines have been extensively researched on the molecular structure, cell signaling and transduction pathway. With respect to cytokine-regulating therapy in immunological imbalance however, the reported results are conflicting because of the pleiotropic functions and the intricate interactions of the cytokine network. In this review, we outline the observations on interleukin-10 (IL-10) upregulatory therapy. Despite varying opinions on its therapeutic effects for different disorders, IL-10 has been considered a potential anti-inflammatory cytokine. Numerous studies support the view that IL-10 shows a strong suppressive effect on Th1 lymphocytes, antigen presenting cells and the production of inflammatory mediators. It is also noticeable that recent research has revealed the relationship between IL-10 induced antigen specific regulatory CD4+ T cells and antigen specific immune tolerance. This specific regulation was mediated in part through IL-10 secretion, because anti-IL-10 treatment reverted the inhibitory effect of regulatory T cell clones. In different models, these cells were shown to inhibit both Th1 and Th2-type inflammatory responses through the secretion of IL-10. With the presence of IL-10, regulatory T cells may induce peripheral immune tolerance. Exogenous administration, transgenic expression and endogenous stimulative agents of IL-10 have been used for a variety of inflammatory diseases, autoimmune diseases and allograft rejection in patients and experimental models. A therapeutic intervention with drug inducing endogenous IL-10 may be more practical than an exogenous administration of IL-10 with transient effect. Although further investigation on gene regulation of IL-10 is necessary, increasing studies have been reported concerning the attempt to develop the agents, which could promote endogenous IL-10 production for the treatment of immunological disorders and inflammatory diseases. With some unclear mechanisms, these agents have strongly upregulated IL-10 production in vitro or in vivo. Reported IL-10 upregulatory agents have shown promising prospects for remission of autoimmune diseases and inflammatory diseases and have even induced antigen specific immune tolerance. It is interesting that the IL-10 upregulatory effect of several traditional immunosuppressive drugs has been detected, e.g. glucocorticoid, which is considered "not more as an immunosuppressive drug but an immune modulating agent". Approximately twenty IL-10 upregulatory agents as instances are described in the present review. In addition, their therapeutic effects in various diseases are discussed.
四十多种细胞因子已在分子结构、细胞信号传导和转导途径方面得到广泛研究。然而，就免疫失衡中的细胞因子调节疗法而言，由于细胞因子网络的多效性功能和复杂相互作用，所报道的结果相互矛盾。在本综述中，我们概述了白细胞介素-10（IL-10）上调疗法的相关观察结果。尽管对于其对不同疾病的治疗效果存在不同观点，但IL-10已被认为是一种潜在的抗炎细胞因子。大量研究支持这样的观点，即IL-10对Th1淋巴细胞、抗原呈递细胞和炎症介质的产生具有强烈的抑制作用。同样值得注意的是，最近的研究揭示了IL-10诱导的抗原特异性调节性CD4 + T细胞与抗原特异性免疫耐受之间的关系。这种特异性调节部分是通过IL-10分泌介导的，因为抗IL-10治疗可逆转调节性T细胞克隆的抑制作用。在不同模型中，这些细胞通过分泌IL-10显示出抑制Th1和Th2型炎症反应的作用。在有IL-10存在的情况下，调节性T细胞可能诱导外周免疫耐受。IL-10的外源性给药、转基因表达和内源性刺激剂已被用于患者和实验模型中的多种炎症性疾病、自身免疫性疾病和同种异体移植排斥反应。用药物诱导内源性IL-10的治疗干预可能比具有短暂效果的IL-10外源性给药更具实用性。尽管有必要对IL-10的基因调控进行进一步研究，但已有越来越多的研究报道了开发能够促进内源性IL-10产生以治疗免疫性疾病和炎症性疾病的药物的尝试。尽管机制尚不清楚，但这些药物在体外或体内强烈上调了IL-10的产生。已报道具有上调IL-10作用的药物在自身免疫性疾病和炎症性疾病的缓解方面显示出有前景的效果，甚至诱导了抗原特异性免疫耐受。有趣的是，已检测到几种传统免疫抑制药物具有IL-10上调作用，例如糖皮质激素，它被认为“不再仅仅是一种免疫抑制药物，而是一种免疫调节剂”。本综述中描述了约二十种作为实例的IL-10上调药物。此外，还讨论了它们在各种疾病中的治疗效果。
