• Anesthesiology · Dec 2013

    Critical Role of Interleukin-11 in Isoflurane-mediated Protection against Ischemic Acute Kidney Injury in Mice.

    • Ahrom Ham, Mihwa Kim, Joo Yun Kim, Kevin M Brown, James Yeh, Vivette D D'Agati, and H Thomas Lee.
    • * Postdoctoral Research Scientist, † Research Associate, ‡ Research Student, ‖ Professor, Department of Anesthesiology, § Professor, Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, New York.
    • Anesthesiology. 2013 Dec 1;119(6):1389-401.

    BackgroundIsoflurane releases renal tubular transforming growth factor-β1 (TGF-β1) and protects against ischemic acute kidney injury. Recent studies suggest that TGF-β1 can induce a cytoprotective cytokine interleukin (IL)-11. In this study, the authors tested the hypothesis that isoflurane protects against ischemic acute kidney injury by direct induction of renal tubular IL-11 synthesis.MethodsHuman kidney proximal tubule cells were treated with 1.25-2.5% isoflurane or carrier gas (room air + 5% carbon dioxide) for 0-16 h. The authors also anesthetized C57BL/6 mice with 1.2% isoflurane or with equianesthetic dose of pentobarbital for 4 h. In addition, the authors subjected IL-11 receptor (IL-11R) wild-type, IL-11R-deficient, or IL-11 neutralized mice to 30-min renal ischemia followed by reperfusion under 4 h of anesthesia with pentobarbital or isoflurane (1.2%).ResultsIsoflurane increased IL-11 synthesis in human (approximately 300-500% increase, N = 6) and mouse (23 ± 4 [mean ± SD] fold over carrier gas group, N = 4) proximal tubule cells that were attenuated by a TGF-β1-neutralizing antibody. Mice anesthetized with isoflurane showed significantly increased kidney IL-11 messenger RNA (13.8 ± 2 fold over carrier gas group, N = 4) and protein (31 ± 9 vs. 18 ± 2 pg/mg protein or approximately 80% increase, N = 4) expression compared with pentobarbital-anesthetized mice, and this increase was also attenuated by a TGF-β1-neutralizing antibody. Furthermore, isoflurane-mediated renal protection in IL-11R wild-type mice was absent in IL-11R-deficient mice or in IL-11R wild-type mice treated with IL-11-neutralizing antibody (N = 4-6).ConclusionIn this study, the authors suggest that isoflurane induces renal tubular IL-11 via TGF-β1 signaling to protect against ischemic acute kidney injury.

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