Protective effect of OK-432 on mice against endotoxemia and infection withPseudomonas aeruginosa and Salmonella enteritidis

OK-432 has been used clinically as a biological response modifier for cance r therapy. We investigated here the protective effects of OK-432 against en dotoxic shock and infectious death caused by Pseudomonas aeruginosa and Sal monella enteritidis in mice and proposed a possible mechanism. Pretreatment of OK-432 reduced the lethality of lipopolysaccharide (LPS)-induced endoto xic shock in D-(+)galactosamine-sensitized C3H/HeN mice. OK-432 did not aff ect the TNF alpha production in blood, but it did decrease the susceptibili ty to TNF alpha. Furthermore, an acceleration of LPS clearance from blood w as detected. The pretreatment of OK-432 also decreased the lethality of mic e in bacterial infection caused by P. aeruginosa and S. enteritidis. The ra pid decrease of the viable bacteria from the circulating blood and in splee n and liver in mice was observed in a manner similar to LPS clearance, Thes e findings indicate that the protective effect of OK-432 against the endoto xemia and bacteremia may depend on an up-regulation of clearance of LPS and bacteria and the augmented resistance to TNF alpha.