Open AccessBLOCKADE OF TUMOR NECROSIS FACTOR REDUCES LIPOPOLYSACCHARIDE LETHALITY, BUT NOT THE LETHALITY OF CECAL LIGATION AND PUNCTURE
Author(s) -
Daniel G. Remick,
Prerana Manohar,
G. Bolgos,
Jorge Luis Rodriguez,
Lyle L. Moldawer,
Gordon K. Wollenberg
Publication year - 1995
Publication title -
shock
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.095
H-Index - 117
eISSN - 1540-0514
pISSN - 1073-2322
DOI - 10.1097/00024382-199508000-00002
Subject(s) - tumor necrosis factor alpha , sepsis , lipopolysaccharide , medicine , antiserum , antibiotics , necrosis , pharmacology , immunology , ligation , microbiology and biotechnology , antibody , biology
Inhibition 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 BALB/c mice. Neutralizing rabbit anti-TNF antisera were evaluated in CD-1 mice by injecting the antisera 3 h before intravenous (i.v.) LPS (600 micrograms). 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 BALB/c mice injected with antisera before LPS (200 micrograms) mortality was reduced (dead/total: control sera, 14/14; anti-TNF, 4/12; p = .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 BALB/c 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.