Ischemia/reperfusion-induced IFN-gamma up-regulation: involvement of IL-12 and IL-18.

M.A.R.C. Daemen, C. van 't Veer, T.G.A.M. Wolfs, W.A. Buurman

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Department of General Surgery, University of Maastricht, The Netherlands.

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.
Original languageEnglish
Pages (from-to)5506-5510
Number of pages5
JournalJournal of Immunology
Volume162
Issue number9
Publication statusPublished - 1 Jan 1999

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