Role of IL-$1{\alpha}$ in Cisplatin-Induced Acute Renal Failure in Mice

Background/Aims: For unknown reasons, caspase-1 -/- mice, protected against cisplatin-induced acute renal failure (ARF), are deficient in interleukin (IL)-$1{\alpha}$. We thus asked whether IL-$1{\alpha}$ deficiency underlies the mechanism of protection against cisplatin-induced ARF in these mice. Methods: Cisplatin (30 mg/kg) was injected intraperitoneally into wild-type C57BL/6 mice to produce a cisplatin-induced model of ARF. IL-$1{\alpha}$ was measured in control vehicle- and cisplatin-treated wild-type animals. We also examined whether IL-$1{\alpha}$ -/- mice were similarly protected against cisplatin-induced ARF. Additionally, infiltration of CD11b- and CD49b-positive cells, as markers of macrophages, natural killer, and natural killer T cells (pan-NK cells), was investigated in wild-type and IL-$1{\alpha}$ -/- mice. Results: Compared with vehicle-treated mice, renal IL-$1{\alpha}$ increased in cisplatin-treated wild-type mice beginning on day 1. IL-$1{\alpha}$ -/- mice were shown to be protected against cisplatin-induced ARF. No significant difference in the infiltration of neutrophils or CD11b- and CD49b-positive cells were observed between wild-type and IL-$1{\alpha}$ -/- mice. Conclusions: Mice deficient in IL-$1{\alpha}$ are protected against cisplatin-induced ARF. The lack of IL-$1{\alpha}$ may explain, at least in part, the protection against cisplatin-induced ARF observed in caspase-1 -/- mice. Investigation of the protective mechanism (s) in IL-$1{\alpha}$ -/- mice in cisplatin-induced ARF merits further study.