O'Garra Anne, Barrat Franck J, Castro Antonio G, Vicari Alain, Hawrylowicz Catherine
Division of Immunoregulation, MRC National Institute for Medical Research, Mill Hill, London, UK.
Immunol Rev. 2008 Jun;223:114-31. doi: 10.1111/j.1600-065X.2008.00635.x.
Interleukin-10 (IL-10) is a cytokine with broad anti-inflammatory properties by its suppression of both macrophage and dendritic cell function, including antigen-presenting cell function and the production of proinflammatory cytokines. This can result subsequently in the feedback regulation of both T-helper 1 (Th1)-type and Th2-type responses. This review discusses the potential use of IL-10 or agents that induce IL-10 as potential anti-inflammatory therapies in inflammatory diseases. Although IL-10-deficient mice develop colitis in the presence of normal gut flora and clear certain intracellular pathogens more efficiently, this is often accompanied by immunopathology, which can be lethal to the host. This reinforces the anti-inflammatory properties of IL-10, although it should be noted that as discussed below, IL-10 can also promote B-cell and other immune responses under particular settings. A penalty of its role to limit the immune and inflammatory responses to pathogens and prevent damage to the host is that high or dysregulated levels of IL-10 may result in chronic infection. Thus, antagonists of IL-10 show great potential as adjuvants in preventative or therapeutic vaccines against chronic infection or cancer. This article reviews basic published studies on IL-10, which may lead to potential uses of IL-10 or its antagonists in human disease.
白细胞介素-10(IL-10)是一种具有广泛抗炎特性的细胞因子,它可抑制巨噬细胞和树突状细胞的功能,包括抗原呈递细胞功能以及促炎细胞因子的产生。这随后可导致对辅助性T细胞1(Th1)型和Th2型反应的反馈调节。本综述讨论了IL-10或诱导IL-10的药物作为炎症性疾病潜在抗炎疗法的潜在用途。尽管IL-10缺陷小鼠在正常肠道菌群存在的情况下会发生结肠炎,并且能更有效地清除某些细胞内病原体,但这通常伴随着免疫病理学改变,这可能对宿主是致命的。这强化了IL-10的抗炎特性,不过应当注意的是,如下文所讨论的,在特定情况下IL-10也可促进B细胞和其他免疫反应。其在限制对病原体的免疫和炎症反应以及防止对宿主造成损害方面所起作用的一个代价是,IL-10水平过高或失调可能导致慢性感染。因此,IL-10拮抗剂作为针对慢性感染或癌症的预防性或治疗性疫苗的佐剂显示出巨大潜力。本文综述了已发表的关于IL-10的基础研究,这些研究可能会带来IL-10或其拮抗剂在人类疾病中的潜在应用。