Enhanced sensitivity to endotoxin induced by 6-sulfanilamidoindazole

6-Sulfanilamidoindazole (6-SAI) is a sulfonamide that induces inflammation in the ankles and hind paws of older rats and sensitizes the animals to the lethal actions of endotoxin. Sensitization is associated with reductions in plasma glucose concentration but not changes in phagocytic function of the RES or increases in lysosomal or hepatic enzymes. Death in 6-SAI-pretreated but not control rats was associated with fibrin deposition in the glomerular capillaries (generalized Shwartzman reaction) and inflamed paws. Endotoxin shock in both 6-SAI-pretreated and control rats was associated with increases in activities of lysosomal and hepatic enzymes and hypoglycemia. Methylprednisolone but not desoxycorticosterone pretreatment protected 6-SAI-fed rats against endotoxin lethality and the generalized Shwartzman reaction and maintained the plasma glucose concentration but did not prevent loss of lysosomal integrity. Simultaneous administrations of small doses of phenylbutazone with 6-SAI suppressed inflammation but did not protect against endotoxin lethality or the generalized Shwartzman reaction.