Circulating IL-6 upregulates IL-10 production in splenic CD4+ T cells and limits acute kidney injury-induced lung inflammation
Circulating IL-6 upregulates IL-10 production in splenic CD4+ T cells and limits acute kidney injury-induced lung inflammation
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DOI：
10.1016/j.kint.2016.12.014
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发表时间：
2017-05-01
影响因子：
19.6
通讯作者：
Faubel, Sarah
中科院分区：
文献类型：
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作者：
Andres-Hernando, Ana;Okamura, Kayo;Faubel, Sarah
虽然急性肾损伤（阿基）是一种促炎状态，但对内源性抗炎反应知之甚少。IL-6传统上被认为是一种促炎细胞因子，其在人和鼠阿基的血清中升高。然而，已知IL-6具有抗炎作用。在这里，我们试图研究IL-6在阿基后的抗炎反应中的作用，特别是关于抗炎细胞因子IL-10。通过双侧肾蒂夹闭诱导缺血性阿基。IL-10缺陷小鼠在阿基后全身和肺部炎症增加，证明了IL-10在限制阿基后炎症中的作用。然后，我们试图确定IL-6是否介导IL-10的产生。患有阿基的野生型小鼠具有脾IL-10的显著上调，这在患有阿基的11-6缺陷小鼠中不存在。在体外，向脾细胞中加入11-6增加了CD 4（+）T细胞、B细胞和巨噬细胞中IL-10的产生。在体内，患有阿基的CD 4缺陷小鼠的脾11-10减少，肺髓过氧化物酶活性增加。因此，IL-6直接增加IL-10的产生并参与阿基后的抗炎反应。
Although it is well established that acute kidney injury (AKI) is a proinflammatory state, little is known about the endogenous counter-inflammatory response. IL-6 is traditionally considered a pro-inflammatory cytokine that is elevated in the serum in both human and murine AKI. However, IL-6 is known to have anti-inflammatory effects. Here we sought to investigate the role of IL-6 in the counter-inflammatory response after AKI, particularly in regard to the anti-inflammatory cytokine IL-10. Ischemic AKI was induced by bilateral renal pedicle clamping. IL-10-deficient mice had increased systemic and lung inflammation after AKI, demonstrating the role of IL-10 in limiting inflammation after AKI. We then sought to determine whether IL-6 mediates IL-10 production. Wild type mice with AKI had a marked upregulation of splenic IL-10 that was absent in 11-6-deficient mice with AKI. In vitro, addition of 11-6 to splenocytes increased IL-10 production in CD4(+) T cells, B cells, and macrophages. In vivo, CD4-deficient mice with AKI had reduced splenic 11-10 and increased lung myeloperoxidase activity. Thus, IL-6 directly increases IL-10 production and participates in the counter-inflammatory response after AKI.