Detrimental Functions of IL-17A in Renal Ischemia-Reperfusion Injury in Mice

Background. Renal ischemia-reperfusion (I/R) injury, as a common and clinically important problem, starts with direct damage caused by chemokines and inflammatory cytokines, which is aggravated by specific and nonspecific immune reactions. Recently, IL-17A has been considered to be in a uniquely powerful position between adaptive and innate immunity. The present study investigated the role of IL-17A in renal I/R injury in mice. Methods. We measured the time-course of changes in plasma and renal IL-17A levels using a murine model of renal I/R injury. Then, the protective effect of monoclonal anti-IL-17A antibody, given intravenously at 30 min before or after renal I/R operation, on renal I/R injury was investigated. In addition, the levels of plasma and renal pro-and anti-inflammatory cytokines and chemokines were assessed. Results. IL-17A was significantly increased in plasma and kidneys after renal I/R injury in mice. Furthermore, intravenous administration of neutralizing monoclonal anti-IL-17A antibody attenuated renal I/R injury by evaluating renal function and histopathology. In addition, administration of anti-IL-17A antibody substantially reduced the plasma and renal levels of many pro-inflammatory mediators (TNF-alpha, IL-6, high-mobility group box1 (HMGB1), IL-1 beta, IL-17A, macrophage inflammatory protein-1 alpha (MIP-1 alpha), and monocyte chemoattractant protein-1 (MCP-1), as well as increased the plasma and renal levels of anti-inflammatory cytokines IL-10 and transforming growth factor beta (TGF-beta). Conclusion. The above data suggest that IL-17A has a detrimental effect on renal I/R injury via facilitating the production of pro-inflammatory cytokines and chemokines as well as hampering the production of anti-inflammatory cytokines. Crown Copyright (C) 2011 Published by Elsevier Inc. All rights reserved.