The role of Macrophage Migration Inhibitory Factor in Critical Illness

Emerging evidence suggests a crucial role for Macrophage Migration Inhibitory Factor (MIF) within the adaptive and innate immune system. In contrast to most cytokines, MIF is stored in preformed cytoplasmatic vesicles of various cell types enabling a rapid release in response to various inflammatory stimuli such as infection, surgical stress, hypoxia, ischemia and reperfusion. MIF acts as key player within the inflammatory cascade and provides several biological functions such as control of cell growth and arrest (activation of ERK1/2), sensing of pathogen stimuli (up regulation of TLR4 expression), inhibition of glucocorticoid induced immunosuppression and prevention of p53-mediated apoptosis of macrophages. The functional role of MIF within inflammation and infection seems however ambiguous: On the one hand, the pro-inflammatory effects of MIF are essential for an effective host defense. On the other hand, an overwhelming MIF release might be associated with organ dysfunction and various deleterious effects. Even more puzzling, recent data indicate a protective role of this pleiotrope cytokine during ischemia and reperfusion. This review focuses on new insights regarding the biological significance of MIF release in the context of critical illness and ischemia/reperfusion.status: publishe