Kurzfassung

Interferon (IFN)- 1, - 2, and - 3 (also designated IL-28A, IL-28B and IL-29) are the latest members of the class II cytokine family and were shown to have potent antiviral activity in vitro and in vivo. Their cellular receptor consists of two chains, the specific IL-28R alpha chain and the IL-10R beta chain, and mediates the tyrosine phosphorylation of STAT transcription factors (most notably STAT1, 2, 3). Recently published data support an unexspected role for the IFN-lambdas in modulating...Interferon (IFN)- 1, - 2, and - 3 (also designated IL-28A, IL-28B and IL-29) are the latest members of the class II cytokine family and were shown to have potent antiviral activity in vitro and in vivo. Their cellular receptor consists of two chains, the specific IL-28R alpha chain and the IL-10R beta chain, and mediates the tyrosine phosphorylation of STAT transcription factors (most notably STAT1, 2, 3). Recently published data support an unexspected role for the IFN-lambdas in modulating the biological activity of cells of both the innate and the adaptive immune system. We could demonstrate in initial studies that IL-28 A and B protein levels were systemically upregulated in mice with septic peritonitis (CLP model). We thus evaluated if the expression/signal transduction of these cytokines has an impact on disease severity by taking advantage of IL-28R gene deficient mice. As a result these knockout mice had a significant survival advantage compared to wildtype control mice. In contrast, mice overexpressing trangenic IL-28A protein displayed lower median survival rates than the controls. Currently, we are evaluating the molecular mechanisms that could explain this potential role of IL-28 expression in the pathogenesis of polymicrobial sepsis. » weiterlesen» einklappen