Lincomycin protects mice from septic shock in β-glucan-indomethacin model

Abstract

We have developed a septic shock model in mice by sequential administration of β-glucan, a biological response modifier, and indomethacin (IND), a nonsteroidal anti-inflammatory drug. Lethality was significantly related to the translocation of gut flora to various organs and mal-adjustment of the cytokine network. In the present study, we have examined the effect of antibiotics on this model to further clarify meanings of microbial flora. Schizophyllan (SPG), antitumor β-glucan for clinical use, obtained from the culture filtrate of Schizophyllum commune, was used to induce sepsis. Lincomycin (LCM), imipenem (IPM), cilastatine (CS), and ampicillin (ABPC) were used for antibiotics treatment. The survival rate of SPG/IND-treated mice was significantly increased by administering LCM or ABPC/IPM/CS, and the effect was more significant by LCM. In in vitro spleen cell culture, LCM decreased proinflammatory cytokine production. Moreover, prednisolone, immune suppresser treatment improved survival of SPG/IND-treated mice. These findings suggest that LCM is an effective antibiotic in this endogenous septic model by modulating gut microbial flora and, at least a part, by regulating cytokine production of leukocytes. © 2007 Pharmaceutical Society of Japan.