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.