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

Ann Intensive Care. 2016 Dec;6(1):56. doi: 10.1186/s13613-016-0157-1. Epub 2016 Jun 22.


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.

Keywords: IL-17A knockout; Sepsis; Sepsis-associated acute kidney injury.