Display options
Share it on

Transl Perioper Pain Med. 2018;5(3):63-74. doi: 10.31480/2330-4871/071. Epub 2018 May 22.

Volatile Anesthetic Isoflurane Attenuates Liver Injury in Experimental Polymicrobial Sepsis Model.

Translational perioperative and pain medicine

Sophia Koutsogiannaki, Hui Zha, Koichi Yuki

Affiliations

  1. Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA.
  2. Department of Anaesthesia, Harvard Medical School, Boston, MA, USA.
  3. Department of Pediatric, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

PMID: 29977977 PMCID: PMC6029873 DOI: 10.31480/2330-4871/071

Abstract

Volatile anesthetics are often administered to patients with sepsis for procedural anesthesia or sedation in intensive care units. Sepsis still carries significant morbidities and mortalities, and organ injuries pose major complications. Early liver dysfunction is associated with poor outcome mainly as a result of overwhelming neutrophil recruitment. Leukocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) are major adhesion molecules on neutrophils and involved in neutrophil recruitment. We have previously showed that volatile anesthetic isoflurane inhibited LFA-1 and Mac-1. Here we studied the role of isoflurane, LFA-1 and Mac-1 on neutrophil recruitment to the liver and liver injury using experimental polymicrobial abdominal sepsis induced by cecal ligation and puncture (CLP) surgery. We used wild type (WT), LFA-1, Mac-1 and intercellular adhesion molecule-1 (ICAM-1) knockout (KO) mice. Following the induction of sepsis by CLP surgery, a group of mice were exposed to isoflurane for 2 hours. We found that Mac-1 and ICAM-1, but not LFA-1 were involved in neutrophil recruitment to liver. Isoflurane attenuated neutrophil recruitment and liver injury in WT and LFA-1 KO mice. Mac-1 KO mice had limited neutrophil recruitment and liver injury, both of which were not attenuated by isoflurane further, suggesting that isoflurane mitigated liver injury via Mac-1. Mac-1 colocalized with ICAM-1 and fibrinogen on liver tissues. In the presence of fibrinogen Mac-1 bound ICAM-1 significantly more, while LFA-1 bound less to ICAM-1, suggesting that Mac-1 used fibrinogen as a bridging molecule to bind ICAM-1. In conclusion, isoflurane exposure attenuated neutrophil recruitment and liver injury via Mac-1.

Keywords: Cecal ligation and puncture; Leukocyte function-associated antigen-1; Liver; Macrophage-1 antigen; Neutrophil

Conflict of interest statement

Conflict of Interest: None.

References

  1. Transplantation. 1993 Jun;55(6):1265-72 - PubMed
  2. FASEB J. 2008 Dec;22(12):4109-16 - PubMed
  3. Immunity. 1996 Dec;5(6):653-66 - PubMed
  4. Am J Respir Crit Care Med. 2016 Jun 1;193(11):1202-12 - PubMed
  5. Toxicol Pathol. 2012;40(2):157-65 - PubMed
  6. Nat Protoc. 2009;4(1):31-6 - PubMed
  7. J Trauma. 2005 Apr;58(4):711-6; discussion 716-7 - PubMed
  8. Cell Tissue Res. 2018 Mar;371(3):589-598 - PubMed
  9. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2215-20 - PubMed
  10. World J Clin Cases. 2015 Sep 16;3(9):793-806 - PubMed
  11. Anesth Analg. 2011 Dec;113(6):1438-41 - PubMed
  12. World J Gastroenterol. 2017 May 7;23(17):3043-3052 - PubMed
  13. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4140-5 - PubMed
  14. J Exp Med. 2008 Apr 14;205(4):915-27 - PubMed
  15. Blood. 2007 Mar 1;109(5):1971-4 - PubMed
  16. Anesthesiology. 2016 Aug;125(2):399-411 - PubMed
  17. Crit Care Med. 2007 May;35(5):1244-50 - PubMed
  18. J Biol Chem. 2004 Oct 22;279(43):44897-906 - PubMed
  19. Toxicol Sci. 2017 Apr 1;156(2):402-411 - PubMed
  20. Annu Rev Physiol. 1995;57:827-72 - PubMed
  21. J Immunol. 2007 Jan 15;178(2):851-7 - PubMed
  22. J Clin Invest. 2004 Jun;113(11):1596-606 - PubMed
  23. Anesth Analg. 2017 Apr;124(4):1190-1199 - PubMed
  24. J Anesth. 2013 Apr;27(2):261-8 - PubMed
  25. J Innate Immun. 2013;5(4):348-57 - PubMed
  26. FASEB J. 2012 Nov;26(11):4408-17 - PubMed
  27. J Biol Chem. 1997 Jan 3;272(1):435-41 - PubMed
  28. Nat Rev Immunol. 2011 Jun;11(6):416-26 - PubMed
  29. Burns Trauma. 2014 Jul 28;2(3):97-105 - PubMed
  30. Lab Invest. 2018 Jan;98(1):51-62 - PubMed
  31. J Surg Res. 1997 Dec;73(2):117-22 - PubMed
  32. Int Rev Immunol. 2014 Nov-Dec;33(6):498-510 - PubMed
  33. Arterioscler Thromb Vasc Biol. 2000 Mar;20(3):652-8 - PubMed
  34. Proc Natl Acad Sci U S A. 1995 Feb 28;92(5):1505-9 - PubMed
  35. Anesthesiology. 2010 Dec;113(6):1439-46 - PubMed
  36. Hepatology. 1993 May;17(5):915-23 - PubMed
  37. Shock. 2012 Jul;38(1):1-3 - PubMed
  38. J Immunol. 2009 Dec 1;183(11):7557-68 - PubMed
  39. Anesth Analg. 2017 Oct;125(4):1355-1363 - PubMed
  40. Am J Respir Crit Care Med. 2017 Mar 15;195(6):792-800 - PubMed
  41. Crit Care Med. 2001 Jul;29(7 Suppl):S42-7 - PubMed
  42. Anesthesiology. 2011 Feb;114(2):363-73 - PubMed
  43. Hepatol Res. 2013 Mar;43(3):255-66 - PubMed
  44. J Immunotoxicol. 2016;13(2):148-56 - PubMed
  45. J Leukoc Biol. 2005 Feb;77(2):129-40 - PubMed
  46. Cell. 1991 Jun 14;65(6):961-71 - PubMed
  47. Shock. 2005 Jul;24(1):40-7 - PubMed
  48. J Immunol. 2013 Apr 15;190(8):4371-81 - PubMed
  49. Transl Perioper Pain Med. 2016;1(2):17-23 - PubMed
  50. Am J Physiol Regul Integr Comp Physiol. 2000 May;278(5):R1140-7 - PubMed
  51. Am J Physiol Gastrointest Liver Physiol. 2001 Aug;281(2):G577-85 - PubMed
  52. J Immunol. 1999 Nov 1;163(9):5029-38 - PubMed
  53. Am J Pathol. 2016 Aug;186(8):2105-2116 - PubMed
  54. Crit Care Med. 2013 Feb;41(2):580-637 - PubMed

Publication Types

Grant support