Role of heat-shock protein 70 in multiple-organ dysfunction syndrome

Abstract

Multiple-organ dysfunction syndrome (MODS) occurs as a result of organ injury caused by an overwhelming, uncontrolled, systemic inflammatory response. Clinical trials aimed at blocking, neutralizing, or removing single inflammatory mediators failed to be effective in preventing or treating MODS, probably due to the multiple redundancies in inflammatory pathways. More recently, research has focused on factors able to act simultaneously on the multiple, redundant parallel systems. Heat-shock protein 70 (HSP70) is one of these factors. Increased expression of HSP70 not only confers protection against oxidative and metabolic stress, but also minimizes the cellular response to pro-inflammatory stimuli, including apoptosis leading to tissue damage and organ failure, observed in MODS. Furthermore, genetic variation in HSP70 production is being increasingly associated with adverse outcomes from a variety of infectious and inflammatory diseases. This review focuses on HSP70 and the evidence for its potential thera...