Knockout of interleukin-17A protects against sepsis-associated acute kidney injury

BACKGROUND: Sepsis-associated acute kidney injury (SA-AKI) is an independent risk factor for death in patients with sepsis, but treatment for it is limited. To improve the diagnosis and treatment of SA-AKI, we must first understand its pathogenesis. Recently, interleukin (IL)-17A has been shown to be associated with the pathogenesis of acute kidney injury and sepsis, but its role in SA-AKI remains unclear. METHODS: SA-AKI was induced in male C57BL/6 and IL-17A(−/−) mice using cecal ligation and puncture (CLP) operations for 24 h. RESULTS: At 7 days, only seven mice survived in the wild-type septic group, but nine survived in the IL-17A(−/−) septic group, corresponding to survival rates of 25 % and 45 %, respectively. At 24 h after CLP operations, both wild-type and IL-17A(−/−) septic mice developed kidney injury. The IL-17A(−/−) septic mice exhibited decreased serum creatinine and blood urea nitrogen levels and an improved acute tubular necrosis score. The IL-17A(−/−) septic mice exhibited decreased IL-6, interferon-γ, tumor necrosis factor-α, CXCL1, CXCL2, and CXCL5 expression in kidney tissue, but increased IL-10 expression. In addition, renal neutrophil infiltration was attenuated significantly in the IL-17A(−/−) septic group. Moreover, IL-17A(−/−) septic mice showed significantly decreased apoptosis of tubular epithelial cells, including decreased TUNEL-positive tubular cell number and cleaved caspase-3 level, compared with the wild-type CLP group. Their Bax/Bcl-2 expression ratio was also increased. CONCLUSIONS: Our study demonstrates that IL-17A knockout could protect against SA-AKI. We show that IL-17A plays a pathogenic role in SA-AKI by increasing the levels of proinflammatory cytokines and chemokines, and by inducing neutrophil infiltration and apoptosis of tubular epithelial cells. Accordingly, IL-17A may be a novel target in SA-AKI. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13613-016-0157-1) contains supplementary material, which is available to authorized users.