Interleukin-10 inhibits ischemic and cisplatin-induced acute renal injury

Background. Acute renal failure (ARF) is caused by ischemic and nephrotoxic insults acting alone or in combination. Anti-inflammatory agents have been shown to decrease renal ischemia-reperfusion and cisplatin-induced injury and leukocyte infiltration. Interleukin-10 (IL-10) is a potent anti-inflamm atory cytokine that inhibits inflammatory and cytotoxic pathways implicated in acute renal injury. Therefore, we sought to determine if IL-10 inhibits acute renal injury. Methods. The effects of IL-10 were studied in mice following cisplatin admi nistration and bilateral renal ischemia-reperfusion, in a rat model of rena l transplantation, and in cultured mouse cortical tubule cells. Results. IL-10 significantly decreased renal injury following cisplatin adm inistration and following renal ischemia/reperfusion. Delay of IL-10 treatm ent for one hour after cisplatin also significantly inhibited renal damage. IL-10 and alpha -melanocyte stimulating hormone (alpha -MSH) increased rec overy following transplantation of a kidney subjected to warm ischemia. To explore the mechanism of action of IL-10, its effects were measured on medi ators of leukocyte trafficking and inducible nitric oxide synthase (NOS-II) . IL-10 inhibited cisplatin and ischemia-induced increases in mRNA for tumo r necrosis factor-a (TNF-alpha), intercellular adhesion molecule-1 (ICAM-1) , and NOS-II. IL-10 also inhibited staining for markers of apoptosis and ce ll cycle activity following cisplatin administration, and nitric oxide prod uction in cultured mouse cortical tubules. Conclusions. IL-10 protects against renal ischemic and cisplatin-induced in jury. IL-10 may act, in part, by inhibiting the maladaptive activation of g enes that cause leukocyte activation and adhesion, and induction of iNOS.