Endogenous IL-10 regulates IFN-γ and IL-5 cytokine production and the granulomatous response in Schistosomiasis mansoni-infected mice
Endogenous IL-10 regulates IFN-γ and IL-5 cytokine production and the granulomatous response in Schistosomiasis mansoni-infected mice
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DOI：
10.1046/j.1365-2567.1998.00544.x
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发表时间：
1998-08-01
期刊：
影响因子：
6.4
通讯作者：
Whitfield, JR
中科院分区：
文献类型：
--
作者：
Boros, DL;Whitfield, JR
在小鼠环卵曼氏血吸虫病中，肉芽肿的形成受促炎和抗炎细胞因子的调节。在后者中，白介素10(IL-10)已被证明具有调节炎症反应的作用。在这项研究中，我们研究了内源性产生的IL-10在辅助性T细胞1(Th1)和Th2型细胞因子的产生和肉芽肿形成中的作用。肉芽肿和脾细胞在感染过程中产生IL-10的动态不同。前者在肉芽肿早期发育阶段(感染后6周)产量达到高峰，然后下降。在肉芽肿反应下调之前，脾细胞的产量在12周时达到顶峰。在肉芽肿发展过程中，巨噬细胞和T细胞均分泌IL-10。在加入抗IL-10单抗的肉芽肿细胞培养中，内源性IL-10对干扰素-γ的调节仅在6周时才表现出来，而IL-2的调节作用持续至整个感染过程(6-20周)。IL-4的产生没有受到影响，但IL-5的产生在6周和8周的时间点被调节。在肉芽肿反应的高峰期(8周)，脾细胞对干扰素-γ和IL-2的产生有调节作用。IL-4的产生不受调节，而IL-5的产生仅在6周时被调节。在感染后6周、12周或20周反复注射抗IL-10单抗可显著促进早期(6周)小鼠肝、肺肉芽肿生长、组织嗜酸性粒细胞增多和干扰素-γ、IL-5的产生。因此，在血吸虫感染的小鼠中，内源性IL-10被证明在免疫反应的早期Th0/Th1阶段调节Th1和Th2型细胞因子的产生和肉芽肿的形成。
In murine Schistosomiasis mansoni circumovum, granuloma formation is regulated by pro- and anti-inflammatory cytokines. Among the latter, interleukin-10 (IL-10) has been shown to regulate the inflammatory response. In this study we examined the role of endogenously produced IL-10 in T-helper 1 (Th1)- and Th2-type cytokine production and granuloma formation. The dynamics of IL-10 production through the course of the infection were different in granuloma versus splenic cells. In the former, production peaked during the early developmental stage (6 weeks of infection) of the granuloma and then declined. In splenocytes production peaked at 12 weeks, before downmodulation of the granuloma response. In the developing granuloma both macrophages and T cells secreted IL-10. In anti-IL-10 monoclonal antibody (mAb)-supplemented granuloma cell cultures endogenous IL-10-mediated regulation of interferon-gamma (IFN-gamma) was manifest only at 6 weeks; that of IL-2 continued throughout the infection (6-20 weeks). IL-4 production was unaffected, but IL-5 production was regulated at the 6 and 8 weeks time point. Splenocytes showed regulation of IFN-gamma and IL-2 production at the peak of the granulomatous response (8 weeks). IL-4 production was not regulated, whereas IL-5 production was regulated only at 6 weeks. Repeated injections of anti-IL-10 mAb given to mice at 6, 12 or 20 weeks of the infection significantly enhanced liver and lung granuloma growth, tissue eosinophilia, and IFN-gamma, IL-5 production at the early developmental phase (6 weeks) of the lesions. Thus, in schistosome-infected mice endogenous IL-10 is shown to regulate Th1- and Th2-type cytokine production and granuloma formation during the early Th0/Th1 phase of the immune response.