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-1Ra) has attenuated ischemic reperfusion injury in brain, heart, and liver models. However, the role of IL-1 in renal ischemic reperfusion injury (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 30 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 absence of IL-1R1 confirmed by DNA blots. IL-1Ra, IL-1R KO, and control groups 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-1R 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 animals, developed significantly less infiltration of polymorphonuclear leukocytes per 10 high-power fields in postischemic renal tissue (1111 +/- 228 and 967 +/- 198 versus 1820 +/- 190, P < 0.05). In contrast to the comparable renal functions at 24 h, recovery of renal function was significantly accelerated in the IL-1R KO group compared with control at 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 that IL-1 is unlikely to be beneficial in the recovery of renal function after ischemia and may play a deleterious role.
Haq
M
M
Department of Internal Medicine, University of South Florida, Tampa, USA.
Norman
J
J
Saba
S R
SR
Ramirez
G
G
Rabb
H
H
D000704:Analysis of Variance; D000818:Animals; D046508:Culture Techniques; D004195:Disease Models, Animal; D007375:Interleukin-1 / Q000378:metabolism*; D007677:Kidney Function Tests; D007683:Kidney Tubular Necrosis, Acute / Q000378:metabolism* / Q000473:pathology; D007684:Kidney Tubules / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D012016:Reference Values; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology
D007375:Interleukin-1; D017472:Receptors, Interleukin-1