title: Critical role of interleukin-11 in isoflurane-mediated protection against ischemic acute kidney injury in mice.
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).
  
  
  CONCLUSIONS
  In this study, the authors suggest that isoflurane induces renal tubular IL-11 via TGF-β1 signaling to protect against ischemic acute kidney injury.
authors.affiliation: * 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.
authors.forename: Ahrom
authors.initials: A
authors.lastname: Ham
authors.forename: Mihwa
authors.initials: M
authors.lastname: Kim
authors.forename: Joo Yun
authors.initials: JY
authors.lastname: Kim
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Brown
authors.forename: James
authors.initials: J
authors.lastname: Yeh
authors.forename: Vivette D
authors.initials: VD
authors.lastname: D'Agati
authors.forename: H Thomas
authors.initials: HT
authors.lastname: Lee
mesh_terms: D058186:Acute Kidney Injury / Q000503:physiopathology / Q000517:prevention & control*; D000704:Analysis of Variance; D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D017370:Interleukin-11 / Q000096:biosynthesis / Q000502:physiology*; D007530:Isoflurane / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D053773:Transforming Growth Factor beta1 / Q000502:physiology; D000099157:Sphingosine Kinase
chemical_list: D018685:Anesthetics, Inhalation; D017370:Interleukin-11; D007530:Isoflurane; D017853:Phosphotransferases (Alcohol Group Acceptor); D053773:Transforming Growth Factor beta1; D000099157:Sphingosine Kinase
references.citation: Am J Physiol Renal Physiol. 2012 Oct 15;303(8):F1216-24
references.pmid: 22859402
references.citation: J Pediatr Hematol Oncol. 2001 Jun-Jul;23(5):300-5
references.pmid: 11464987
references.citation: Kidney Int. 2008 Jun;73(11):1220-30
references.pmid: 18322542
references.citation: Am J Physiol Renal Physiol. 2008 Feb;294(2):F371-8
references.pmid: 18057187
references.citation: Cytokine Growth Factor Rev. 2006 Feb-Apr;17(1-2):19-27
references.pmid: 16290023
references.citation: Circulation. 2010 Feb 9;121(5):684-91
references.pmid: 20100971
references.citation: Kidney Int. 2013 Jul;84(1):90-103
references.pmid: 23423261
references.citation: Transplantation. 1983 Mar;35(3):198-204
references.pmid: 6340272
references.citation: Am J Physiol Renal Physiol. 2008 Jul;295(1):F128-36
references.pmid: 18434384
references.citation: Am J Physiol. 1999 Jan;276(1):L175-85
references.pmid: 9887070
references.citation: Am J Physiol Renal Physiol. 2007 Sep;293(3):F713-22
references.pmid: 17596528
references.citation: Am J Physiol Renal Physiol. 2006 Jul;291(1):F67-78
references.pmid: 16478975
references.citation: J Histochem Cytochem. 2000 Feb;48(2):303-12
references.pmid: 10639497
references.citation: Am J Physiol Renal Physiol. 2007 Dec;293(6):F1827-35
references.pmid: 17898040
references.citation: Am J Physiol Renal Physiol. 2010 Apr;298(4):F1041-50
references.pmid: 20053797
references.citation: N Engl J Med. 1997 Apr 10;336(15):1066-71
references.pmid: 9091804
references.citation: Stem Cells. 1996;14 Suppl 1:256-60
references.pmid: 11012229
references.citation: Contrib Nephrol. 2010;165:153-158
references.pmid: 20427965
references.citation: J Pharmacol Sci. 2011;117(4):213-22
references.pmid: 22056652
references.citation: Acta Clin Belg. 2007;62 Suppl 2:326-31
references.pmid: 18283993
references.citation: Anesthesiology. 2012 May;116(5):1139-48
references.pmid: 22415388
references.citation: Am J Nephrol. 2010;31(4):353-62
references.pmid: 20234131
references.citation: J Am Soc Nephrol. 2004 Jan;15(1):102-11
references.pmid: 14694162
references.citation: Kidney Int. 2009 Mar;75(5):499-510
references.pmid: 19020532
references.citation: Anesthesiology. 2011 Feb;114(2):363-73
references.pmid: 21245730
references.citation: Blood. 1997 Jun 1;89(11):3897-908
references.pmid: 9166826
references.citation: J Immunol. 1996 Oct 15;157(8):3627-34
references.pmid: 8871663
references.citation: Oncology (Williston Park). 2000 Sep;14(9 Suppl 8):32-40
references.pmid: 11033836
references.citation: J Investig Dermatol Symp Proc. 2006 Sep;11(1):112-7
references.pmid: 17069018
references.citation: Exp Biol Med (Maywood). 2009 Oct;234(10):1186-91
references.pmid: 19596824
references.citation: J Am Soc Nephrol. 2001 Nov;12(11):2310-2320
references.pmid: 11675407
references.citation: Am J Nephrol. 2007;27(4):416-24
references.pmid: 17622749
references.citation: Scand J Clin Lab Invest. 1965;17(4):381-7
references.pmid: 5838275
references.citation: J Am Soc Nephrol. 2005 Nov;16(11):3365-70
references.pmid: 16177006
references.citation: Anesthesiology. 2004 Dec;101(6):1313-24
references.pmid: 15564938
references.citation: Am J Physiol Gastrointest Liver Physiol. 2003 Sep;285(3):G529-38
references.pmid: 12760902
references.citation: J Clin Invest. 2002 Jan;109(1):41-50
references.pmid: 11781349
references.citation: Am J Physiol Renal Physiol. 2004 Feb;286(2):F298-306
references.pmid: 14600029
references.citation: Am J Physiol Gastrointest Liver Physiol. 2008 Mar;294(3):G728-37
references.pmid: 18202115
references.citation: Anesthesiology. 2013 Jun;118(6):1446-54
references.pmid: 23558177
references.citation: Cytokine. 2007 May;38(2):107-15
references.pmid: 17629706
references.citation: Gastroenterology. 2003 May;124(5):1358-68
references.pmid: 12730876
references.citation: J Nephrol. 2011 Jan-Feb;24(1):106-11
references.pmid: 20640990
references.citation: J Am Soc Nephrol. 2013 Oct;24(10):1558-70
references.pmid: 23813214
references.citation: Kidney Int. 1994 Jan;45(1):48-57
references.pmid: 8127021
references.citation: Hepatology. 1999 Dec;30(6):1441-7
references.pmid: 10573523
references.citation: Natl Health Stat Report. 2009 Jan 28;(11):1-25
references.pmid: 19294964
references.citation: J Clin Invest. 1990 Dec;86(6):1976-84
references.pmid: 2254455
references.citation: Minerva Urol Nefrol. 2009 Sep;61(3):171-88
references.pmid: 19773721
references.citation: Lab Invest. 2010 Aug;90(8):1209-24
references.pmid: 20458275
references.citation: J Biol Chem. 1998 Mar 6;273(10):5506-13
references.pmid: 9488674
references.citation: Am J Respir Cell Mol Biol. 2003 Oct;29(4):513-22
references.pmid: 12730073
references.citation: Am J Physiol. 1999 Nov;277(5):L861-7
references.pmid: 10564168
references.citation: J Surg Res. 2002 Dec;108(2):268-72
references.pmid: 12505051
references.citation: Am J Physiol. 1981 Oct;241(4):F403-11
references.pmid: 6119031
references.citation: J Immunol. 1997 Dec 1;159(11):5661-70
references.pmid: 9548510