Ischemia/reperfusion-induced IFN-gamma up-regulation: involvement of IL-12 and IL-18.
Tissue injury as a consequence of ischemia followed by reperfusion is characterized by early as well as late signs of inflammation. The latter, among others, involves IFN-gamma-dependent up-regulation of MHC class I and II Ag expression. Employing a murine model of renal ischemia, we show that renal IL-18 mRNA up-regulation coincides with caspase-1 activation at day 1 following ischemia. IFN-gamma and IL-12 mRNA are subsequently up-regulated at day 6 following ischemia. Combined, but not separate, in vivo neutralization of the IFN-gamma inducing cytokines IL-12 and IL-18 reduces IFN-gamma-dependent MHC class I and II up-regulation to a similar extent as IFN-gamma neutralization, suggesting the involvement of functional IL-12, IL-18, and IFN-gamma protein. These results reveal a novel relationship between tissue injury of nonmicrobial origin and the induction of IL-12 as well as IL-18. The collaboration observed between endogenous IL-12 and IL-18 in the induction of IFN-gamma after renal ischemia/reperfusion, resembles the immune response to bacterial infections.
Daemen
M A
MA
Department of General Surgery, University of Maastricht, The Netherlands.
van't Veer
C
C
Wolfs
T G
TG
Buurman
W A
WA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D002465:Cell Movement / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology*; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D020382:Interleukin-18 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D007511:Ischemia / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000098:blood supply* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D013997:Time Factors; D015854:Up-Regulation / Q000276:immunology*
D000911:Antibodies, Monoclonal; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D020382:Interleukin-18; D018664:Interleukin-12; D007371:Interferon-gamma