The Renal Level of a Novel Cytokine IL-35 Is Related to Sepsis-Associated Acute Kidney Injury in Mice

: Interleukin-35 (IL-35) is a novel immunosuppressive and anti-inflammatory cytokine. IL-35 is mainly secreted by regulatory T cells (Tregs), and exerts its effects through inducing proliferation of Tregs and reducing activity of helper T cells Th17. However, the effect of IL-35 on sepsis-associated acute kidney injury (SA-AKI) remains unclear. This study is aimed to examine the expression and role of IL-35 in an animal model of SA-AKI induced by cecal ligation and puncture (CLP). Eleven C57 male mice with SA-AKI and eight controls were used, and blood and kidney tissues were collected. Blood creatinine (Cr), urea nitrogen (BUN), alanine transaminase (ALT) and aspartate transaminase (AST) were measured to assess kidney and liver injury. The renal morphology and cell apoptosis were examined. The mRNA and protein expression levels of IL-35 in kidney tissues were tested by qRT-PCR, IHC-P, IF, and ELISA. Biochemical and histological examinations indicated CLP induced SA-AKI in mice. TUNEL assay showed apoptosis of renal tubular epithelial cells in SA-AKI mice. The mRNA and protein expression of IL-12α and EBI3 in kidney tissues decreased significantly in SA-AKI mice compared with those in sham controls. IL-35 levels in kidney tissues displayed a significantly negative correlation with the levels of Cr (r = -0.584, P = 0.009), ALT (r = -0.549, P = 0.015), AST (r = -0.475, P = 0.04), but not with BUN (r = -0.437, P = 0.061). These results demonstrated that IL-35 is associated with the pathological process of SA-AKI, and might represent a potential therapeutic agent for SA-AKI treatment.