Protective effect of OK-432 on mice against endotoxemia and infection with Pseudomonas aeruginosa and Salmonella enteritidis.
OK-432 has been used clinically as a biological response modifier for cancer therapy. We investigated here the protective effects of OK-432 against endotoxic shock and infectious death caused by Pseudomonas aeruginosa and Salmonella enteritidis in mice and proposed a possible mechanism. Pretreatment of OK-432 reduced the lethality of lipopolysaccharide (LPS)-induced endotoxic shock in D-(+)-galactosamine-sensitized C3H/HeN mice. OK-432 did not affect the TNFalpha production in blood, but it did decrease the susceptibility to TNFalpha. Furthermore, an acceleration of LPS clearance from blood was detected. The pretreatment of OK-432 also decreased the lethality of mice in bacterial infection caused by P. aeruginosa and S. enteritidis. The rapid decrease of the viable bacteria from the circulating blood and in spleen and liver in mice was observed in a manner similar to LPS clearance. These findings indicate that the protective effect of OK-432 against the endotoxemia and bacteremia may depend on an up-regulation of clearance of LPS and bacteria and the augmented resistance to TNFalpha.
Hashimoto
M
M
Department of Infectious Diseases and Tropical Medicine, Research Institute, International Medical Center of Japan, Tokyo.
Kirikae
F
F
Toyooka
K
K
Kaneko
A
A
Yamasu
H
H
Iwai
H
H
Nakano
M
M
Kirikae
T
T
D000818:Animals; D016470:Bacteremia / Q000188:drug therapy*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D019446:Endotoxemia / Q000188:drug therapy*; D005260:Female; D008070:Lipopolysaccharides / Q000009:adverse effects / Q000097:blood; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010844:Picibanil / Q000494:pharmacology / Q000627:therapeutic use*; D011552:Pseudomonas Infections / Q000097:blood / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012480:Salmonella Infections / Q000097:blood / Q000188:drug therapy*; D012477:Salmonella enteritidis / Q000187:drug effects; D012772:Shock, Septic / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000494:pharmacology
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D010844:Picibanil