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Polymyxin B Reduces Total Parenteral Nutrition-Associated Hepatic Steatosis by Its Antibacterial Activity and by Blocking Deleterious Effects of Lipopolysaccharide

Department of Surgery, Hebrew University-Hadassah Medical School, Jerusalem, Israel

Herve Bercovier, DVM

Department of Medicine, Hebrew University-Hadassah Medical School, Jerusalem, Israel

Elliot M. Berry, MD

Department of Clinical Microbiology, Hebrew University-Hadassah Medical School, Jerusalem, Israel

Yosef Haviv, BSc

Department of Surgery, Hebrew University-Hadassah Medical School, Jerusalem, Israel

Ruth Gallily, MSC, PHD

Department of Lautenberg Center for General and Tumor Immunology, Hebrew University-Hadassah Medical School, Jerusalem, Israel

Herbert R. Freund, MD

Department of Surgery, Hebrew University-Hadassah Medical School, Jerusalem, Israel

Overgrowth of Gram-negative bacteria as a result of total parenteral nutrition (TPN) and bowel rest could be responsible for the release of a variety of hepatotoxic substances such as endotoxin or tumor necrosis factor (TNF) and the ensuing TPN-associated liver function derangements. Polymyxin B is an effective antimicrobial agent as well as a blocking agent for endotoxin (lipopolysaccharide) activity and TNF production. In the present study we compared the oral and intravenous effects of polymyxin in rats receiving TPN in an attempt to define these two possible mechanisms of action of polymyxin on TPN-associated hepatic steatosis.

Both oral, as well as intravenous polymyxin B, significantly reduced total hepatic fat and triglyceride accumulation in TPN rats, more so in the intravenous group exhibiting close to control levels. Both polymyxin-treated groups exhibited significantly lower Gram-negative bacterial counts in the cecum, with the oral group exhibiting a lower count than the IV group. The spontaneous production of TNF by peritoneal macrophages was markedly increased in rats receiving TPN and very close to being undetected in both groups receiving TPN and polymyxin.

We believe polymyxin B protects the liver during TPN by both its antimicrobial effect which prevents overgrowth of gut Gram-negative bacteria and the subsequent translocation of endotoxin, and by its specific antilipopolysaccharide activity which, in the present study, completely abolished hepatic steatosis and TNF production during TPN. (Journal of Parenteral and Enteral Nutrition 16:529-532, 1992)

Journal of Parenteral and Enteral Nutrition, Vol. 16, No. 6, 529-532 (1992)
DOI: 10.1177/0148607192016006529


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