The RAGE axis in systemic inflammation, acute lung injury and myocardial dysfunction: an important therapeutic target?

Intensive Care Medicine
Benedict C Creagh-BrownAnne Burke-Gaffney

Abstract

The sepsis syndromes, frequently complicated by pulmonary and cardiac dysfunction, remain a major cause of death amongst the critically ill. Targeted therapies aimed at ameliorating the systemic inflammation that characterises the sepsis syndromes have largely yielded disappointing results in clinical trials. Whilst there are many potential reasons for lack of success of clinical trials, one possibility is that the pathways targeted, to date, are only modifiable very early in the course of the illness. More recent approaches have therefore attempted to identify pathways that could offer a wider therapeutic window, such as the receptor for advanced glycation end-products (RAGE) and its ligands. The objectives of this study were to review the evidence supporting the role of the RAGE axis in systemic inflammation and associated acute lung injury and myocardial dysfunction, to explore some of the problems and conflicts that these RAGE studies have raised and to consider strategies by which they might be resolved. MEDLINE was searched (1990-2010) and relevant literature collected and reviewed. RAGE is an inflammation-perpetuating receptor with a diverse range of ligands. Evidence supporting a role of the RAGE axis in the pathogenesi...Continue Reading

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