Papel da citocina MIF em modelos de respostas inflamatórias sistêmicas

Abstract

Macrophage Migration Inhibitory Factor (MIF) is a potent pro-inflammatory cytokine, which may induce TNF- release and play an important role in innate immune and inflammatory responses. The aim of this work was to assess the role of MIF in two murine models of systemic inflammatory responses: intestinal ischemia and reperfusion (I/R) and dengue infection. There was an increase in circulating levels of MIF in both animal models. After I/R, vascular permeability, hemorrhage and production of TNF- in the intestine and lungs were lower in MIF-deficient (MIF-/-) than in wild type (WT) mice.Lethality was partially prevented in MIF-/- mice. The reperfusion-associated neutrophil accumulation in the intestine and lungs was similar in WT and MIF-/- mice. Thus, MIF mediates tissue injury and lethality but not the influx of neutrophils, suggesting thar aneffect on the activation of neutrophils, rather than on recruitment, mediates the effects of MIF in the system. In an experimental model of Dengue infection, MIF-/- mice showed reduced levels of cytokines and chemokines, and prevention of infection-associated hemoconcentration and thrombocytopenia. The latter findings were associated with adelayed lethality in MIF-/- mice, but all animals eventually succumbed to the infection. IN conclusion, our results suggest that there is production of MIF during systemic inflammation. More importantly, it appears that MIF plays an important role in the pathogenesis of both eperfusion-associated injury and lethality and dengue infection.Blockers of MIF function may provide an interesting therapeutic approach for the treatment of diseases with a systemic inflammatory component.