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Anesthesiology:
doi: 10.1097/ALN.0b013e3182a950da
Critical Care Medicine

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

Ham, Ahrom Ph.D.*; Kim, Mihwa Pharm.D.; Kim, Joo Yun Ph.D.*; Brown, Kevin M. B.S.; Yeh, James B.S.; D’Agati, Vivette D. M.D.§; Lee, H. Thomas M.D.

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Abstract

Background: Isoflurane 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.
Methods: Human 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%).
Results: Isoflurane 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).
Conclusion: In this study, the authors suggest that isoflurane induces renal tubular IL-11 via TGF-β1 signaling to protect against ischemic acute kidney injury.

© 2013 American Society of Anesthesiologists, Inc.

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