The impact of RAGE inhibition in animal models of bacterial sepsis: a systematic review and meta-analysis

Objective To evaluate the impact of inhibition of the receptor for advanced glycation end products (RAGE) on the outcome of bacterial sepsis in animal models. Methods Relevant publications were identified by systematic searches of PubMed, ISI Web of Science and Elsevier-Scopus databases. Results A total of Eleven studies with moderate quality were selected for analysis. A meta-analysis of survival rates revealed a significant advantage of RAGE inhibition in comparison with controls (HR 0.67, 95% CI 0.52-0.86). This effect was most pronounced in polymicrobial infection (HR 0.28, 95% CI 0.14-0.55), followed by Gram positive (G(+)) bacterial infection (HR 0.70, 95% CI 0.50-0.97) and Gram negative (G(-)) bacterial infection (HR 0.89, 95% CI 0.58-1.38). For G(+) bacterial infection, RAGE inhibition decreased bacterial outgrowth and dissemination, inflammatory cell influx, plasma cytokine levels, and pulmonary injury. Conclusions RAGE inhibition appears to have a beneficial impact on the outcome of sepsis in animal models, although there are discrepancies between different types of infection.