Co-exposure of lipopolysaccharide and pseudomonas aeruginosa exotoxin A-induced multiple organ injury in rats

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 μg/kg LPS plus 10 μg/kg PEA developed severe liver, kidney, and lung injury; elevation of TNF-α, IFN-γ, 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.

Keywords::

• Cytokines
• lipopolysaccharide
• multiple organ injury
• pseudomonas aeruginosa exotoxin A

Acknowledgments

The authors are grateful to Mr. Yu-Hsiang Lin and Ms. Shiou-Ling Lia for technical assistance. This study was supported in part by Grant NSC 92-2313-B-492–002 from the National Science Council, Taiwan.