Receptor for advanced glycation end products in bacterial infection: Is there a role for immune modulation of receptor for advanced glycation end products in the treatment of sepsis?

Abstract

Purpose of review: Sepsis is still associated with excess morbidity and mortality worldwide, despite significant advances in critical care medicine. A novel approach is needed in the treatment of sepsis, one that will aim to correct the specific immunologic imbalance that is detrimental to the septic host. Recent findings: As receptor for advanced glycation end products (RAGE) is involved in diverse cellular mechanisms that to a lesser or greater extent participate in the septic process, modulating its function could favorably affect outcome. Altering RAGE may result in regulating the release of proinflammatory cytokines, controlling apoptosis or modifying endothelial architecture. In that regard, several strategies have been used to study RAGE deficiency in experimental models of sepsis including antibodies against RAGE, genetically deleted RAGE knockouts, siRNA to silence RAGE, soluble forms of RAGE, and antibodies and inhibitors directed toward RAGE ligands, such as HMGB1 and S100 proteins. Summary: These studies thus far have yielded inconsistent results as to whether RAGE is beneficial or not to the host response during bacterial infection and sepsis. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.