Effects of immunomodulation with interferon-gamma on hepatic ischemia-reperfusion injury.
The development of an inflammatory response after injury depends on the participation of a variety of cell populations and endogenous mediators. Interferon-gamma (IFN-gamma) is a potent cellular immunomodulating cytokine that contributes to acute and chronic inflammation. In this study, the effects of immunomodulation on ischemia-reperfusion injury were examined using increasing doses of recombinant, rabbit-specific IFN-gamma in an in situ model of hepatic ischemia-reperfusion. Pretreatment with low dose IFN-gamma augmented injury as measured by histology, aminotransferase concentrations, and myeloperoxidase activity. By contrast, high dose IFN-gamma pretreatment, equivalent to IFN-gamma supplements used in clinical trials, resulted in a lack of neutrophil infiltration and minimal progression of late phase, neutrophil-mediated reperfusion injury. These results suggest that immunomodulating mediators such as IFN-gamma may play a regulating role in the evolution of ischemia-reperfusion, contributing to the development and resolution of acute hepatic injury.
Langdale
L A
LA
Department of Surgery, University of Washington, Seattle 98195, USA.
Wilson
L
L
Jurkovich
G J
GJ
Liggitt
H D
HD
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D007371:Interferon-gamma / Q000627:therapeutic use*; D008099:Liver / Q000098:blood supply*; D051379:Mice; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins; D015427:Reperfusion Injury / Q000188:drug therapy*
D000276:Adjuvants, Immunologic; D011994:Recombinant Proteins; D007371:Interferon-gamma; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase