Fibrates ameliorate the course of bacterial sepsis by promoting neutrophil recruitment via CXCR2.

ABSTRACT: Bacterial sepsis results in high mortality rates, and new therapeutics to control infection are urgently needed. Here, we investigate the therapeutic potential of fibrates in the treatment of bacterial sepsis and examine their effects on innate immunity. Fibrates significantly improved the survival from sepsis in mice infected with Salmonella typhimurium, which was paralleled by markedly increased neutrophil influx to the site of infection resulting in rapid clearance of invading bacteria. As a consequence of fibrate-mediated early control of infection, the systemic inflammatory response was repressed in fibrate-treated mice. Mechanistically, we found that fibrates preserve chemotaxis of murine neutrophils by blocking LPS-induced phosphorylation of ERK. This results in a decrease of G prot

SUBMITTER: Tancevski I 

PROVIDER: S-EPMC4203357 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature