| Literature DB >> 12271144 |
Heidrun Koebernick1, Leander Grode, John R David, Wolfgang Rohde, Michael S Rolph, Hans-Willi Mittrücker, Stefan H E Kaufmann.
Abstract
The cytokine macrophage migration inhibitory factor (MIF) exerts a multitude of biological functions. Notably, it induces inflammation at the interface between the immune system and the hypothalamus-pituitary-adrenal stress axis. The role of MIF in infectious diseases is not understood completely. Here, we show that MIF-deficient (MIF(-/-)) knockout mice fail to control an infection with wild-type Salmonella typhimurium. Increased susceptibility was accompanied by a reduced Th1 response, demonstrated by decreased levels of IL-12, IFNgamma, and tumor necrosis factor alpha. In Salmonella-infected MIF(-/-) mice, levels of IL-1beta were markedly increased. Additionally, infected MIF(-/-) mice showed elevated serum levels of nitric oxide and corticosterone as compared with control mice. Our results point to MIF as a key mediator in the host response to S. typhimurium. MIF not only promotes development of a protective Th1 response but ameliorates disease by altering levels of reactive nitrogen intermediates and corticosteroid hormones, which both exert immunosuppressive functions.Entities:
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Year: 2002 PMID： 12271144 PMCID： PMC129741 DOI： 10.1073/pnas.212488699
Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205