ABSTRACTInhibition of tumor necrosis factor (TNF) bioactivity has afforded protection in several animal models of sepsis. We examined whether inhibition of TNF could improve survival after lethal lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in CD-1 or BALBc mice. Neutralizing rabbit anti-TNF antisera were evaluated in CD-1 mice by injecting the antisera 3 h before intravenous (i.v.) LPS (600mu;g). Implantable radiotransmitters were used for continuous monitoring of temperature. No decrease in mortality was observed, and the anti-TNF failed to prevent the drop in temperature. In BALBc mice injected with antisera before LPS (200mu;sg) mortality was reduced (dead/totalcolon; control sera, 14/14; anti-TNF, 4/12;pequals; .007 control sera vs. anti-TNF). CD-1 mice were pretreated with anti-TNF or control sera; CLP was performed followed by administration of antibiotics. Anti-TNF did not decrease pulmonary neutrophil sequestration, improve survival, or prevent the decrease in temperature observed as sepsis developed. CLP was performed in the BALBc mice using antibiotics plus anti-TNF antisera, but no protection was observed. Our results demonstrate that anti-TNF treatment prevents LPS mortality only when using certain strains of mice and inhibition of TNF fails to reduce mortality in a more clinically relevant model of sepsis.
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