Endotoxin toxicity in rats with 6-sulfanilamidoindazole arthritis

Seven oral administrations of 6-sulfanilamidoindazole (6-SAI) to 10- to 12-month-old rats sensitized the animals to endotoxin, with dosages as small as 2.5 microgram causing death in 80% of animals. Endotoxin in a dosage of 3,000 microgram was not lethal for nonmedicated control animals. 6-SAI-treated 1-month-old rats were not as sensitive to endotoxin as aged animals. The sulfonamide-induced sensitivity to endotoxin could not be passively transferred and could not be explained by blockade of the reticuloendothelial system or impairment of endotoxin detoxification. 6-SAI administration was associated with both depletion of liver glycogen and lowering of blood glucose concentration without changes in blood lactic acid concentration. Disseminated intravascular coagulation is believed to be involved in the pathogenesis of shock and death as evidenced by: (i) concomitant decreases in plasma fibrinogen concentration and elevations in fibrin degradation products after endotoxin challenge; (ii) protection against lethal actions of endotoxin by pretreatment with heparin. Treatment of 6-SAI-medicated rats with glucocorticoids before endotoxin challenge protected the animals against lethal doses of endotoxin and prevented deposition of fibrin thrombi in the glomerular capillaries.