Role of cytokines in the formation and downregulation of hepatic circumoval granulomas and hepatic fibrosis in Schistosoma mansoni-infected mice
Role of cytokines in the formation and downregulation of hepatic circumoval granulomas and hepatic fibrosis in Schistosoma mansoni-infected mice
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DOI：
10.1590/s0074-02761998000700004
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发表时间：
1998-01-01
影响因子：
2.8
通讯作者：
Wynn, TA
中科院分区：
文献类型：
--
作者：
Cheever, AW;Jankovic, D;Wynn, TA
曼氏血吸虫感染与强烈的Th2细胞因子反应有关。给小鼠静脉注射IL-12或抗IL-2或抗IL-4。注射鸡蛋增加了干扰素-γ的产生，下调了Th2反应和肺肉芽肿大小。相反，抗干扰素-伽马抗体治疗增加了Th2应答和肉芽肿大小。类似的操作在感染的小鼠身上产生了不那么戏剧性的结果。然而，感染前用鸡蛋+IL-12致敏小鼠可增强Th1应答，降低Th2细胞因子、肉芽肿大小和纤维化。IL-12免疫期间的抗血清可部分恢复感染后肉芽肿的大小和纤维化。急性(8周)感染时肉芽肿大小的变化可能主要受T细胞的数量和激活状态的影响。在慢性(12-16周)感染中，无功能CD8+细胞的小鼠和干扰素-γ-KO小鼠的免疫下调正常进行，而B细胞KO(MuMT)小鼠和FCR表达缺陷的小鼠则不正常，尽管这些小鼠下调了T细胞和细胞因子的反应。显然，细胞因子参与肉芽肿的形成和调节是复杂的，控制这两种现象的机制可能涉及T细胞和抗体/FCR的相互作用。
Schistosoma mansoni infections are associated with a strong Th2 cytokine response. Treatment of mice with IL-12 or anti-IL-2 or anti-IL-4 before i.v. injection of eggs increased IFN-gamma production and downregulated Th2 responses and pulmonary granuloma size. Conversely, anti-IFN-gamma antibody treatment increased Th2 responses and granuloma size. Similar manipulation produced less dramatic results in infected mice. However, sensitization of mice with eggs + IL-12 before infection augmented the Th1 response and decreased Th2 cytokines, granuloma size and fibrosis. Antisera to IFN-gamma, TNF-alpha or IL-12 during IL-12-egg immunization partly restored granuloma size and fibrosis following infection.Variations in the size of granulomas in acute (8 week) infections may be influenced primarily by the number and state of activation of T cells. In chronic (12-16 week) infections immunologic downmodulation proceeded normally in mice without functional CD8+ cells and in IFN-gamma KO mice but not in B cell KO (mu MT) mice or in mice deficient in FcR expression in spite of the fact that these mice downregulated their T cell and cytokine responses. It is evident that the participation of cytokines in granuloma formation and regulation is complicated and that the mechanisms controlling both these phenomena are likely to involve both T cells and antibody/FcR interactions.