Heme sensitization to TNF-Mediated programmed cell death

Abstract

The cytotoxic effect of tumor necrosis factor (TNF) is repressed in most cell types through the expression of several immediate-early TNF-responsive cytoprotective genes. To the best of our knowledge, there are no molecules produced under pathophysiologic condition that have been shown to override this cytoprotective effect. Identification of such molecules should contribute to our current understanding of the mechanisms underlying the pathophysiologic effects of TNF. We will argue that free heme acts in such a manner, promoting TNF-driven cytotoxicity, which might be an important component of the pathogenesis of several immune-mediated inflammatory diseases, as illustrated hereby for malaria. © 2011 Springer Science+Business Media, LLC.