Co-exposure of lipopolysaccharide and Pseudomonas aeruginosa exotoxin A-induced multiple organ injury in rats.
Pseudomonas aeruginosa Exotoxin A (PEA) induces hepatotoxicity in experimental animals. Lipopolysaccharide (LPS) interacts synergistically with xenotoxics to induce severe organ injury. We examined the combination of non-injurious doses of LPS and sub-hepatotoxic PEA in the induction of multiple organ injury (MOI). Rats treated with 20 or 40 microg/kg LPS plus 10 microg/kg PEA developed severe liver, kidney, and lung injury; elevation of TNF-alpha, IFN-gamma, and IL-2; and high mortality. Depletion of Kupffer cells or T-cells by pretreatment with Gadolinium Chloride or FK506, respectively, attenuated MOI. Thus LPS + PEA acted synergistically on Kupffer and T-cells to induce proinflammatory cytokines contributing to MOI.
Chiu
Chien-Chao
CC
Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
Huang
Yen-Te
YT
Chuang
Hsiao-Li
HL
Chen
Hans Hsien-Chuan
HH
Chung
Tung-Ching
TC
D036002:ADP Ribose Transferases / Q000494:pharmacology*; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001219:Aspartate Aminotransferases / Q000097:blood; D001427:Bacterial Toxins / Q000494:pharmacology*; D001806:Blood Urea Nitrogen; D003404:Creatinine / Q000097:blood; D016207:Cytokines / Q000097:blood; D004357:Drug Synergism; D005098:Exotoxins / Q000494:pharmacology*; D005682:Gadolinium / Q000494:pharmacology / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007728:Kupffer Cells / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects; D016559:Tacrolimus / Q000494:pharmacology / Q000627:therapeutic use; D037521:Virulence Factors / Q000494:pharmacology*; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000410:Alanine Transaminase; D000893:Anti-Inflammatory Agents; D001219:Aspartate Aminotransferases; D001427:Bacterial Toxins; D003404:Creatinine; D016207:Cytokines; D005098:Exotoxins; D005682:Gadolinium; D008070:Lipopolysaccharides; D016559:Tacrolimus; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C038958:gadolinium chloride