Limitation of polymyxin B on suppression of endotoxin shock induced by Salmonella infection in mice.
The protective effects of an antibiotic polymyxin B (PLB), having lipopolysaccharide (LPS)-binding activity, on infection-induced endotoxin shock in mice were investigated. Infection with 10(8) colony forming units of an attenuated Salmonella typhimurium aroA strain caused lethal endotoxin shock to ddY mice. Treatment with PLB 1 h post infection (p.i.) resulted in significant reduction of mortality and bacterial numbers in livers. In addition, treatment with PLB 1 h p.i. resulted in a transient increase at the early stage and gradual decline in plasma LPS levels. Although plasma levels of sCD14 and high mobility group box chromosomal protein-1 (HMGB-1) increased according with progression of infection, increases in plasma levels of sCD14 and HMGB-1 were downregulated by treatment with PLB 1 h p.i. However, the lethal shock was not blocked by treatment with anti-CD14 monoclonal antibody at 3 h and 6 h p.i. Interestingly, administration of PLB 6 h p.i. did not show any protective activities, indicating that a time window for effective PLB action is present.
Morita
Hiroyuki
H
Seikagaku Corporation, Tokyo, Japan.
Hasunuma
Ryoichi
R
Kawaguchi
Kiichiro
K
Adachi
Yoshiyuki
Y
Tanaka
Shigenori
S
Kumazawa
Yoshio
Y
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D005260:Female; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008070:Lipopolysaccharides / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D011112:Polymyxin B / Q000494:pharmacology* / Q000627:therapeutic use; D012481:Salmonella Infections, Animal / Q000382:microbiology / Q000517:prevention & control*; D012486:Salmonella typhimurium / Q000187:drug effects*; D012772:Shock, Septic / Q000517:prevention & control*; D013997:Time Factors
D000900:Anti-Bacterial Agents; D024243:HMGB1 Protein; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D011112:Polymyxin B