BLOCKADE OF TUMOR-NECROSIS-FACTOR REDUCES LIPOPOLYSACCHARIDE LETHALITY, BUT NOT THE LETHALITY OF CECAL LIGATION AND PUNCTURE

Inhibition of tumor necrosis factor (TNF) bioactivity has afforded pro tection in several animal models of sepsis. We examined whether inhibi tion of TNF could improve survival after lethal lipopolysaccharide (LP S) or cecal ligation and puncture (CLP) in CD-1 or BALB\c mice. Neutra lizing rabbit anti-TNF antisera were evaluated in CD-1 mice by injecti ng the antisera 3 h before intravenous (i.v.) LPS (600 mu g). Implanta ble radiotransmitters were used for continuous monitoring of temperatu re. 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 mu g) mortality was reduced (dead/total: control sera , 14/14; anti-TNF, 4/12; p = .007 control sera vs. anti-TNF). CD-1 mic e were pretreated with anti-TNF or control sera; CLP was performed fol lowed by administration of antibiotics. Anti-TNF did not decrease pulm onary neutrophil sequestration, improve survival, or prevent the decre ase in temperature observed as sepsis developed. CLP was performed in the BALB\c mice using antibiotics plus anti-TNF antisera, but no prote ction was observed. Our results demonstrate that anti-TNF treatment pr events LPS mortality only when using certain strains of mice and inhib ition of TNF fails to reduce mortality in a more clinically relevant m odel of sepsis.