tacrolimus and gadolinium-chloride

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.

Topics: ADP Ribose Transferases; Alanine Transaminase; Animals; Anti-Inflammatory Agents; Aspartate Aminotransferases; Bacterial Toxins; Blood Urea Nitrogen; Creatinine; Cytokines; Drug Synergism; Exotoxins; Gadolinium; Kidney; Kupffer Cells; Lipopolysaccharides; Liver; Lung; Male; Multiple Organ Failure; Pseudomonas aeruginosa Exotoxin A; Rats; Rats, Wistar; Survival Rate; T-Lymphocytes; Tacrolimus; Virulence Factors