D. Remick et al., BLOCKADE OF TUMOR-NECROSIS-FACTOR REDUCES LIPOPOLYSACCHARIDE LETHALITY, BUT NOT THE LETHALITY OF CECAL LIGATION AND PUNCTURE, Shock, 4(2), 1995, pp. 89-95
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.