Andres-Hernando, AnaOkamura, KayoBhargava, RheaKiekhaefer, Carol M.Soranno, Danielle E.Kirkbride-Romeo, Lara A.Gil, Hyo-wookAltmann, ChrisFaubel, Sarah2022-08-012022-08-012017-05Andres-Hernando A, Okamura K, Bhargava R, et al. Circulating IL-6 upregulates IL-10 production in splenic CD4+ T cells and limits acute kidney injury-induced lung inflammation. Kidney Int. 2017;91(5):1057-1069. doi:10.1016/j.kint.2016.12.014https://hdl.handle.net/1805/29682Although 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 IL-6-deficient mice with AKI. In vitro, addition of IL-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 IL-10 and increased lung myeloperoxidase activity. Thus, IL-6 directly increases IL-10 production and participates in the counter-inflammatory response after AKI.en-USPublisher PolicyAcute kidney injuryCytokinesIschemic reperfusionArticle