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 in the CAR-sensitized group than in the D-GalN-sensitized group.
Franks
A K
AK
Casualty Care Research Department, Naval Medical Research Institute, Bethesda, Maryland 20889-5055.
Kujawa
K I
KI
Yaffe
L J
LJ
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology; D002351:Carrageenan / Q000494:pharmacology; D004195:Disease Models, Animal; D004351:Drug Resistance; D004361:Drug Tolerance; D005260:Female; D005688:Galactosamine / Q000494:pharmacology; D015850:Interleukin-6 / Q000276:immunology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D012772:Shock, Septic / Q000209:etiology* / Q000378:metabolism; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism
D000906:Antibodies; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D002351:Carrageenan