Inhibition of tumor necrosis factor-α release in rat experimental endotoxemia by treatment with the 21-aminosteroid U-74389G

Objective: To determine the effect of the 21-aminosteroid U-74389G on tumor necrosis factor (TNF)-α release in experimental endotoxemia. Design: Prospective, randomized, controlled animal study. Setting: Experimental laboratory. Subjects: Twenty-one male Wistar rats weighing 190 ± 40 g. Interventions: The rats were divided equally into 3 groups: a) control; b) endotoxemia (5 mg/kg lipopolysaccharide [LPS] from Escherichia coli 055:B5); and c) endotoxemia and U-74389G administration 30 rains before (3 mg/kg) and 60 rains after (1.5 mg/kg) endotoxin challenge. Measurements and Main Results: At 0, 120, and 240 mins, serum levels of TNF-α were measured using a specific rat TNF-α ELISA kit. U-74389G-treated endotoxemic animals showed significantly reduced TNF-α release 120 mins after endotoxin challenge (control, 2.5 ± 2.1 pg/mL; LPS, 4041 ± 871 pg/mL; U-74389G, 1627 ± 474 pg/mL [p < .05]). Two hundred forty minutes after LPS administration, TNF-α levels decreased, whereas values in the untreated LPS group remained twice as high as those in the U-74389G group (LPS, 863 ± 182 pg/mL; U-74389G, 369 ± 54 pg/mL [p < .05]). Conclusions: The study demonstrated that administration of U-74389G, which has radical-scavenging and membrane-stabilizing properties, decreased TNF-α release during endotoxemia. Thus, 21- aminosteroids may lend themselves to evaluation in the treatment of septic states.