Trasylol (aprotinin) decreases kidney Interleukin-1beta (IL-1beta) and IL-6 levels following renal ischemia and reperfusion injury

Introduction. Acute renal failure (ARF) may be an ominous complication of circulatory arrest in cardiac surgical patients. Aprotinin is used as a therapeutic adjunct to preserving hemostasis by inhibiting protease-mediated fibrinolysis. Aprotinin has been shown to possess anti-inflammatory properties, which may be renal protective. However, it is unknown whether aprotinin decreases renal proinflammatory cytokine production following I/R. Indeed, other agents which have reduced renal IL-1beta and IL-6 have protected renal function in this setting. We hypothesized that aprotinin would decrease renal IL-1beta and IL-6 production following I/R. Methods. Adult male rats were subjected to unilateral I/R with varying lengths of both ischemia and reperfusion, with and without clinically relevant dosing and administration of aprotinin prior to the insult (clinically aprotinin is given prior to circulatory arrest). At various time points, the kidneys were harvested and the tissue homogenates were assayed for IL-1beta and IL-6 (ELISA). All experiments were approved by the Indiana University Animal Care and Use Committee (IACUC). Results. One-hour ischemia and 2 h of reperfusion significantly increased renal tissue IL-1beta and IL-6 levels (P < 0.05 versus sham, ANOVA with Bonferroni/Dunn). Aprotinin significantly (P < 0.05) decreased renal IL-1beta and IL-6 levels at this time point. Aprotinin also significantly decreased renal IL-1beta at the 1 h ischemia/4 h reperfusion time point. At no point did aprotinin increase production of either cytokine. Conclusions. Aprotinin decreases renal proinflammatory cytokine production following I/R. Further study will be needed to determine if aprotinin decreases renal tubular apoptosis and acute renal failure following such conditions. If so, aprotinin may be useful as an adjunct to preserving renal function following diverse planned ischemic events.