ROLE OF IL-1 IN RENAL ISCHEMIC REPERFUSION INJURY

Interleukin-1 (IL-1) is a central component of many acute inflammatory processes. Blocking IL-1 receptor (IL-1R) with IL-1R antagonist (IL-1 Ra) has attenuated ischemic reperfusion injury in brain, heart, and li ver models. However, the role of IL-1 in renal ischemic reperfusion in jury (IRI) is not known. Therefore, the role of IL-1 in renal IRI was evaluated using the complementary approaches of IL-1R blockade in wild -type mice in addition to the study of renal IRI in IL-1R knockout (KO ) mice. Ischemia was induced by bilateral renal pedicle clamping for 3 0 min. IL-1Ra was administered at 10 mg/kg every 4 h, high doses that have been protective in previous organ injury models in mice. IL-1R KO animals, previously characterized as insensitive to IL-1, had the abs ence of IL-1R1 confirmed by DNA blots. IL-1Ra, IL-1R KO, and control g roups had similar elevations of blood urea nitrogen (114 +/- 13, 133 /- 11, and 120 +/- 11 mg/dl) and serum creatinine (1.7 +/- 0.3, 2.1 +/ - 0.2, and 1.6 +/- 0.3 mg/dl) 24 h after ischemia. Furthermore, acute tubular necrosis scores were also similar in IL-1Ra-treated mice (3.0 +/- 0.3), IL-IR KO mice (2.7 +/- 0.3), and control mice (3.1 +/- 0.2). However, both IL-1Ra and IL-1R KO groups, compared with control anima ls, developed significantly less infiltration of polymorphonuclear leu kocytes per 10 high-power fields in postischemic renal tissue(1111 +/- 228 and 967 +/- 198 versus 1820 +/- 190, P < 0.05). In contrast to th e comparable renal functions at 24 h, recovery of renal function was s ignificantly accelerated in the IL-1R KO group compared with control a t both 48 (P < 0.05) and 72 (P < 0.05) h. Recovery in the IL-1Ra group was similar to that in the control animals. These data demonstrate th at IL-1 is unlikely to be beneficial in the recovery of renal function after ischemia and may play a deleterious role.