Role of Cytokines and Chemokines in Renal Ischemia-Reperfusion Injury.

Cytokines and chemokines produced by renal tubular epithelial cells and infiltrated cells are critical factors in inflammatory processes of renal ischemia-reperfusion injury. In vitro studies reveal that renal tubular epithelial cells have the potential to produce diverse cytokines, chemokines and other mediators, such as tumor necrosis factor-alpha, interleukin-1 (IL-1), monocyte chemoattractant protein-1, IL-8, platelet-derived growth factor, regulated upon activation, normal T cell expressed and secreted, endothelin-1 and vascular endothelial growth factor (VEGF). Huge numbers of in vivo studies show that cytokines, chemokines and adhesion molecules in diseased kidney together govern critical aspects of ischemia-reperfusion injury. Leukocyte­endothelial cell interactions are critical processes of leukocytic infiltration, which are pathologically key factors in inflammatory processes of renal ischemia-reperfusion injury. Leukocyte­endothelial interactions are regulated by a cascade of molecular steps of cytokines, chemokines and adhesion molecules. In contrast, the intracellular cascades of cytokine and chemokine expression in the renal ischemia-reperfusion injury remain to be investigated. p38 mitogen-activated protein kinase is one of the essential mediators in cytokine and chemokine expression through the activation of nuclear factor-kappaB and activating protein-1. Moreover, hypoxia-inducible factor-1 (HIF-1) is a transcription factor activated by reductions in oxygen concentration. HIF-1­related gene expression, such as erythropoietin or VEGF, results in protection of ischemia reperfusion injury. This review focuses on the contribution of cytokines, chemokines and their related molecules to the inflammatory cascade in renal ischemia-reperfusion injury. (c) 2002 Prous Science. All rights reserved.