Role of IL-1 in renal ischemic reperfusion injury

Mahmudul Haq, James Norman, Sabiha R. Saba, German Ramirez, Hamid Rabb

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)614-619
Number of pages6
JournalJournal of the American Society of Nephrology
Volume9
Issue number4
StatePublished - Apr 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Nephrology

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    Haq, M., Norman, J., Saba, S. R., Ramirez, G., & Rabb, H. (1998). Role of IL-1 in renal ischemic reperfusion injury. Journal of the American Society of Nephrology, 9(4), 614-619.