Therapy with antibody to tumor necrosis factor against endotoxin shock in rabbits

The purpose of this study was to determine the efficacy of treatment with anti-tumor necrosis factor (TNF) antibody in preventing the deleterious effects of endotoxin. Polyclonal anti-TNF antibody was produced by immunizing rabbits. Experiments were carried out on 16 rabbits intravenously infused with the lethal dose of lipopolysaccharide (LPS). Pretreatment with anti-TNF antibody resulted in protection from the development of hypotension and metabolic acidosis. The serum TNF level was significantly depressed in the antibody-pretreated group. Eighty-eight percent in the anti-TNF antibody-pretreated rabbits survived more than 48 h, whereas none of the rabbits who were given LPS alone survived over 24 h (LPS group). Prominent histopathological changes in the liver and kidney were evident in the LPS group. In contrast, pathologic changes in the tissue from the anti-TNF antibody group were considerably less prominent. These results support the idea that TNF plays a central role in mediating the pathophysiologic changes during endotoxin shock.