Bacterial translocation is downregulated by anti-TNF-alpha monoclonal antibody administration in rats with cirrhosis and ascites

J Hepatol. 2007 May;46(5):797-803. doi: 10.1016/j.jhep.2006.11.018. Epub 2006 Dec 27.

Abstract

Background/aims: TNF-alpha is involved in the development of bacterial translocation in rats with cirrhosis. The aim of the current study was to evaluate the effect of anti-TNF-alpha mAb treatment on the incidence of bacterial translocation and systemic infections in rats with cirrhosis and ascites.

Methods: Thirty rats with cirrhosis and ascites were randomly assigned to receive two intraperitoneal doses of anti-TNF-alpha mAb, distilled water or immunoglobulin on days 0 and 4. On day 10, a laparotomy was performed.

Results: One out of 11 animals receiving anti-TNF-alpha mAb treatment, 7 out of 10 of the placebo group (p<0.01), and 5 out of 9 of the IgG group developed bacterial translocation (p<0.05). A significantly reduced number of systemic infections were observed in animals receiving anti TNF-alpha mAb treatment vs animals receiving placebo (p<0.01). TNF-alpha in serum at laparotomy in animals receiving anti-TNF-alpha mAb was higher than that in the rest of groups and was also higher in the overall series of animals showing bacterial translocation.

Conclusions: In the experimental model of CCl(4)-induced rat with cirrhosis and ascitic fluid, anti-TNF-alpha mAb administration decreases the incidence of bacterial translocation, in a TNF-alpha/sTNF-alpha receptor-independent manner, without increasing the risk of systemic infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Ascitic Fluid / microbiology
  • Bacterial Translocation / drug effects*
  • Bacterial Translocation / immunology
  • Carbon Tetrachloride
  • Disease Models, Animal
  • Down-Regulation
  • Injections, Intraperitoneal
  • Liver Cirrhosis, Experimental / chemically induced
  • Liver Cirrhosis, Experimental / complications*
  • Liver Cirrhosis, Experimental / drug therapy*
  • Male
  • Peritonitis / microbiology*
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Sepsis / microbiology
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Antibodies, Monoclonal
  • Tumor Necrosis Factor-alpha
  • Carbon Tetrachloride