IL-10 and TGF-beta redundantly protect against severe liver injury and mortality during acute schistosomiasis.
IL-10 and TGF-beta redundantly protect against severe liver injury and mortality during acute schistosomiasis.
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DOI：
10.4049/jimmunol.181.10.7214
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发表时间：
2008-11-15
期刊：
影响因子：
--
通讯作者：
Finkelman FD
中科院分区：
文献类型：
--
作者：
Herbert DR;Orekov T;Perkins C;Finkelman FD
细胞因子IL-10和TGF-β调节免疫和炎症。已知IL-10可抑制曼氏血吸虫自然感染期间寄生虫卵引起的肝损伤程度，但TGF-β的作用尚不清楚。小鼠中的细胞因子阻断研究显示，急性感染期间抗IL-10 R mAb治疗适度增加细胞因子产生和肝损伤，而选择性抗TGF-β mAb治疗具有边际效应。相比之下，尽管CD 4 + CD 25 + Foxp 3 + T调节细胞数量增加，但给予两种mAb的小鼠在感染后8周发生了严重的肝脏炎症，伴有扩大的坏死性肝脏肉芽肿、恶病质和>80%的死亡率。在产卵开始时阻断IL-10和TGF-β也显著增加IL-4、IL-6、TNF、IFN-γ和IL-17的产生，并显著增加肝脏、腹膜和脾脏嗜中性粒细胞。相比之下，抗IL-10 R和TGF-β mAb的联合给药对寄生虫卵诱导的肠道病理学或抑制肠道病理学所需的交替活化巨噬细胞的发育几乎没有影响。这表明在急性S.通过两种不同的器官特异性机制：TGF-β和IL-10冗余地抑制肝脏炎症，而肠道炎症由交替激活的巨噬细胞调节。
The cytokines IL-10 and TGF-β regulate immunity and inflammation. IL-10 is known to suppress the extent of hepatic damage caused by parasite ova during natural infection with Schistosoma mansoni, but the role of TGF-β is less clear. Cytokine blockade studies in mice revealed that anti-IL-10R mAb treatment during acute infection modestly increased cytokine production and liver damage, whereas selective anti-TGF-β mAb treatment had marginal effects. In contrast, mice administered both mAbs developed severe hepatic inflammation, with enlarged, necrotic liver granulomas, cachexia, and >80% mortality by 8 wk postinfection, despite increased numbers of CD4+CD25+Foxp3+ T regulatory cells. Blocking both IL-10 and TGF-β at the onset of egg production also significantly increased IL-4, IL-6, TNF, IFN-γ, and IL-17 production and markedly increased hepatic, peritoneal, and splenic neutrophilia. In contrast, coadministration of anti-IL-10R and TGF-β mAbs had little effect upon parasite ova-induced intestinal pathology or development of alternatively activated macrophages, which are required to suppress intestinal pathology. This suggests that inflammation is controlled during acute S. mansoni infection by two distinct, organ-specific mechanisms: TGF-β and IL-10 redundantly suppress hepatic inflammation while intestinal inflammation is regulated by alternatively activated macrophages.
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