Is macrophage migration inhibitory factor (MIF) the "control point" of vascular hypo-responsiveness in septic shock?

Macrophage migration inhibitory factor (MIF), a member of the cytokine family, is beginning to be recognized as a pleiotropic proinflammatory molecule. MIF exerts function via antagonistic regulation of glucocorticoids, inhibition to apoptosis-mediated p53, influence on vasodilator gas NO and inducible nitric oxide synthase (iNOS), feedback counter-regulation of complement C5a controlling MIF release, and interaction with major cations as well. Interestingly, aforementioned glucocorticoids, apoptosis, NO, iNOS, C5a, Ca2+, Mg2+, Na+, K+, and H+ that are greatly associated with vascular tone or vasomotion. Nevertheless, the elevated serum and cytosolic concentrations of MIF exactly affect all above facets in septic shock models and patients, during which vasodilation of the peripheral resistance vessels occurs, and accompanied with decreased responsiveness to vascular pressors. Thus MIF may bring into play as one of point-controlling proteins in the onset of sustained vascular hypo-reactivity during the process of septic shock.