Lipopolysaccharide‐neutralizing antibody reduces hepatocyte injury from acute hepatotoxin administration

Mark J. Czaja, Jun Xu, Yue Ju, Elaine Alt, Phyllis Schmiedeberg

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Endogenous lipopolysaccharide has been implicated as a cofactor in the hepatocellular injury and death resulting from toxic liver injury. To prevent this lipopolysaccharide‐induced injury and to further understand the mechanism of this effect, an anti‐lipopolysaccharide antibody was administered to rats in which toxic hepatocellular injury was induced. Rats were given the hepatotoxin galactosamine together with an isotypic control antibody B55 or the anti‐lipopolysaccharide antibody E5. E5 treatment resulted in reductions of serum AST levels of 43% at 36 hr (p<0.02) and 60% at 48 hr (NS) after galactosamine administration. These decreases in AST values were accompanied by diminished histological evidence of injury and inflammation. In carbon tetrachloride‐induced liver injury, E5 similarly reduced serum AST levels at 36 and 48 hr by 47% (p<0.04) and 54% (p<0.03), respectively. E5 treatment was equally effective in reducing AST levels 48 hr after administration of carbon tetrachloride, whether the initial dose of antibody was given 1 hr before or 3 or 6 hr after the administration of this toxin. To understand the mechanism of this E5 effect, the activation of the toxic cytokine tumor necrosis factor‐α and the chemotactic cytokine monocyte chemoattractant protein 1 was examined by Northern‐blot analysis of RNA from rat livers after galactosamine‐induced injury and treatment with B55 or E5. Despite E5's efficacy in reducing hepatocellular damage, E5 treatment did not affect the timing or magnitude of tumor necrosis factor‐α or monocyte chemoattractant protein 1 activation during galactosamine‐induced injury. These data suggest that antibody neutralization of lipopolysaccharide may be an effective therapy for toxic liver injury and that the mechanism of this effect is not through the prevention of cytokine expression. (HEPATOLOGY 1994;19:1282–1289.)

Original languageEnglish (US)
Pages (from-to)1282-1289
Number of pages8
Issue number5
StatePublished - May 1994
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology


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