Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP Ribose Transferases / pharmacology*
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Alanine Transaminase / blood
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Animals
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Anti-Inflammatory Agents / pharmacology
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Anti-Inflammatory Agents / therapeutic use
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Aspartate Aminotransferases / blood
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Bacterial Toxins / pharmacology*
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Blood Urea Nitrogen
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Creatinine / blood
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Cytokines / blood
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Drug Synergism
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Exotoxins / pharmacology*
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Gadolinium / pharmacology
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Gadolinium / therapeutic use
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Kidney / drug effects
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Kidney / pathology
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Kupffer Cells / drug effects
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Lipopolysaccharides / pharmacology*
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Liver / drug effects
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Liver / pathology
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Lung / drug effects
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Lung / pathology
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Male
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Multiple Organ Failure / blood
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Multiple Organ Failure / chemically induced*
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Multiple Organ Failure / pathology
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Multiple Organ Failure / prevention & control
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Pseudomonas aeruginosa Exotoxin A
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Rats
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Rats, Wistar
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Survival Rate
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T-Lymphocytes / drug effects
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Tacrolimus / pharmacology
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Tacrolimus / therapeutic use
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Virulence Factors / pharmacology*
Substances
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Anti-Inflammatory Agents
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Bacterial Toxins
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Cytokines
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Exotoxins
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Lipopolysaccharides
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Virulence Factors
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Gadolinium
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Creatinine
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ADP Ribose Transferases
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Aspartate Aminotransferases
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Alanine Transaminase
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gadolinium chloride
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Tacrolimus