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Up-Regulation: Involvement of IL-12 and IL-181
Department of General Surgery, University of Maastricht, 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-
-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- and IL-12
mRNA are subsequently up-regulated at day 6 following ischemia.
Combined, but not separate, in vivo neutralization of the IFN-
inducing cytokines IL-12 and IL-18 reduces IFN--dependent MHC class
I and II up-regulation to a similar extent as IFN- neutralization,
suggesting the involvement of functional IL-12, IL-18, and IFN-
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- after renal ischemia/reperfusion, resembles
the immune response to bacterial infections.
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