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

J Int Med Res. 2018 Jan;46(1):11-21. doi: 10.1177/0300060517713856. Epub 2017 Jul 31.

Abstract

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.

Keywords: Receptor for advanced glycation end products; meta-analysis; sepsis; systematic review.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / therapeutic use*
  • Cytokines / blood
  • Cytokines / genetics
  • Cytokines / immunology
  • Disease Models, Animal
  • Female
  • Gene Expression Regulation
  • Gram-Negative Bacterial Infections / drug therapy*
  • Gram-Negative Bacterial Infections / genetics
  • Gram-Negative Bacterial Infections / microbiology
  • Gram-Negative Bacterial Infections / pathology
  • Gram-Positive Bacterial Infections / drug therapy*
  • Gram-Positive Bacterial Infections / genetics
  • Gram-Positive Bacterial Infections / microbiology
  • Gram-Positive Bacterial Infections / pathology
  • Host-Pathogen Interactions*
  • Humans
  • Mice
  • Mice, Knockout
  • Receptor for Advanced Glycation End Products / antagonists & inhibitors*
  • Receptor for Advanced Glycation End Products / blood
  • Receptor for Advanced Glycation End Products / genetics
  • Receptor for Advanced Glycation End Products / immunology
  • Sepsis / drug therapy*
  • Sepsis / genetics
  • Sepsis / microbiology
  • Sepsis / pathology

Substances

  • Ager protein, mouse
  • Anti-Bacterial Agents
  • Cytokines
  • Receptor for Advanced Glycation End Products