Role of IL-4 and IFN-gamma in Schistosoma mansoni egg-induced hypersensitivity granuloma formation. Orchestration, relative contribution, and relationship to macrophage function.
Role of IL-4 and IFN-gamma in Schistosoma mansoni egg-induced hypersensitivity granuloma formation. Orchestration, relative contribution, and relationship to macrophage function.
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IL-4 和 IFN-γ 在曼氏血吸虫卵诱导的过敏性肉芽肿形成中的作用。
DOI：
10.4049/jimmunol.148.3.900
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发表时间：
1992
影响因子：
4.4
通讯作者：
G. Higashi
中科院分区：
文献类型：
--
作者：
S. Chensue;P. Terebuh;K. Warmington;S. D. Hershey;H. Evanoff;S. Kunkel;G. Higashi
我们建立了一个由曼氏血吸虫卵诱导的T细胞介导的超敏性肉芽肿炎症模型，以评估IL-4和ifn - γ在肉芽肿发展中的作用。在疾病的剧烈期（8周）和调节期（20周）诱导和分离曼氏梭菌感染小鼠的同步肺肉芽肿。确定了IL-4和IFN的顺序产生，并与肉芽肿巨噬细胞产生IL-1、TNF和超氧阴离子（O2-）的时间变化有关。在旺盛期，IL-4在肉芽肿形成的第1天和第2天产生，而IFN在第4天至第8天释放最多。IL-4的峰值出现在IL-1峰值（1天）和最大TNF生成（8至16天）之间的窗口。最大氧释放倾向于与IFN产生平行。在炎症反应减弱的调节阶段，IL-4的产生以及IL-1和TNF的水平显著降低，但IFN的产生持续存在，最大的O2（-）产生能力只是延迟了开始。使用IL-4和IFN特异性mAb来检测这些细胞因子在体内消耗对肉芽肿发展的影响。在8天的研究期间，对同时发生肉芽肿的小鼠给予单剂量1.0 mg的抗il -4抗体，可显著减少肉芽肿的大小（面积抑制40%至50%），而IFN抗体对肉芽肿的大小没有影响。然而，后一种处理减少了巨细胞的形成。我们的研究结果表明，肉芽肿的发展涉及细胞因子的协调生产，可能是由于不同的细胞群的顺序参与。此外，IL-4是健忘症细胞募集的关键细胞因子，受内源性调节。
A well defined model of T cell-mediated hypersensitivity-type granulomatous inflammation induced by Schistosoma mansoni eggs was used to assess the role of IL-4 and IFN-gamma in granuloma development. Synchronized pulmonary granulomas were induced and isolated from S. mansoni-infected mice during vigorous (8 wk) and modulated (20 wk) stages of the disease. The sequential production of IL-4 and IFN was determined and related to temporal changes in granuloma macrophage production of IL-1, TNF, and superoxide anion (O2-). During the vigorous stage, IL-4 was produced on days 1 and 2 of granuloma formation, whereas IFN was released in greatest amounts on days 4 to 8. The peak of IL-4 occurred in a window between the peak of IL-1 (1 day) and maximal TNF production (8 to 16 days). Maximal O2- release tended to parallel IFN production. During the modulated stage when the inflammatory response is attenuated, IL-4 production was dramatically reduced as were levels of IL-1 and TNF, but IFN production persisted and maximum O2(-)-producing capacity was only delayed in onset. mAb specific for IL-4 and IFN were used to examine the effect of in vivo depletion of these cytokines on granuloma development. Administration of a single 1.0-mg dose of anti-IL-4 antibodies to mice with synchronously developing granulomas dramatically reduced granuloma size (40 to 50% suppression of area) during an 8-day study period, whereas antibodies to IFN had no effect on size. However, the latter treatment reduced giant cell formation. Our results indicate that granuloma development involves an orchestrated production of cytokines possibly resulting from sequential participation of different Th cell populations. Moreover, IL-4 is a pivotal cytokine in anamnestic cellular recruitment and subject to endogenous regulation.