EXPERIMENTAL ELIMINATION OF TUMOR-NECROSIS-FACTOR IN LOW-DOSE ENDOTOXIN MODELS HAS VARIABLE EFFECTS ON SURVIVAL

Tumor necrosis factor alpha (TNF) is thought to play a major role in the pathogenesis of septic shock. Anti-TNF antibody was preadministered in low-dose endotoxin lethality models in which BALB/c mice were challenged with small amounts of lipopolysaccharide following their sensitization with either carrageenan (CAR) or D-galactosamine (D-GalN). Although the antibody virtually eliminated circulating TNF in both the CAR and the D-GalN models, only the D-GalN model mice were afforded survival, adding to a growing body of evidence that substances other than TNF play a key role in endotoxin-induced lethality. Further examination of sera from these mice showed a much greater elevation of interleukin-6 levels of the CAR-sensitized group than in the D-GalN-sensitized group.