%0 Journal Article %A Sarah Faubel %A Eli C. Lewis %A Leonid Reznikov %A Danica Ljubanovic %A Thomas S. Hoke %A Hilary Somerset %A Dong-Jin Oh %A Lawrence Lu %A Christina L. Klein %A Charles A. Dinarello %A Charles L. Edelstein %T Cisplatin-Induced Acute Renal Failure Is Associated with an Increase in the Cytokines Interleukin (IL)-1β, IL-18, IL-6, and Neutrophil Infiltration in the Kidney %D 2007 %R 10.1124/jpet.107.119792 %J Journal of Pharmacology and Experimental Therapeutics %P 8-15 %V 322 %N 1 %X We have demonstrated that caspase-1-deficient (caspase-1–/–) mice are functionally and histologically protected against cisplatin-induced acute renal failure (ARF). Caspase-1 exerts proinflammatory effects via the cytokines interleukin (IL)-1β, IL-18, IL-6, and neutrophil recruitment. We sought to determine the role of the cytokines IL-1β, IL-18, and IL-6 and neutrophil recruitment in cisplatin-induced ARF. We first examined IL-1β; renal IL-1β increased nearly 2-fold in cisplatin-induced ARF and was reduced in the caspase-1–/– mice. However, inhibition with IL-1 receptor antagonist (IL-1Ra) did not attenuate cisplatin-induced ARF. Renal IL-18 increased 2.5-fold; however, methods to inhibit IL-18 using IL-18 antiserum and transgenic mice that overproduce IL-18-binding protein (a natural inhibitor of IL-18) did not protect. Renal IL-6 increased 3-fold; however, IL-6-deficient (IL-6–/–) mice still developed cisplatin-induced ARF. We next examined neutrophils; blood neutrophils increased dramatically after cisplatin injection; however, prevention of peripheral neutrophilia and renal neutrophil infiltration with the neutrophil-depleting antibody RB6-8C5 did not protect against cisplatin-induced ARF. In summary, our data demonstrated that cisplatin-induced ARF is associated with increases in the cytokines IL-1β, IL-18, and IL-6 and neutrophil infiltration in the kidney. However, inhibition of IL-1β, IL-18, and IL-6 or neutrophil infiltration in the kidney is not sufficient to prevent cisplatin-induced ARF. The American Society for Pharmacology and Experimental Therapeutics %U https://jpet.aspetjournals.org/content/jpet/322/1/8.full.pdf