Antibiotics protect against septic shock in mice administered beta-glucan and indomethacin.

Abstract

We have developed an animal model of sepsis in mice by repeatedly administering beta-glucan, a biological response modifier, and indomethacin (IND), a nonsteroidal anti-inflammatory drug. The combination of these drugs induced bacteremia by translocation of the enterobacterial flora, resulting in increasing the number of activated leukocytes, and inducing hyper cytokinemia. In the present study, we examined the effect of antibiotics on beta-glucan and IND-induced septic shock. Treatment with antibiotics inhibited microbial translocation, inhibited contraction of the colon, reduced lipopolysaccharides (LPS)-elicited production of TNF-alpha and IL-6, and finally prolonged survival. However, the efficacy of antibiotics treatment was limited in mice administered IND orally. These findings strongly suggested that the antibiotics controlled the gut-associated action of IND and reduced various symptoms accompanying sepsis.