Objective: To determine the effect of the 21-aminosteroid U-74389G on tumor necrosis factor (TNF)-alpha 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 mins before (3 mg/kg) and 60 mins after (1.5 mg/kg) endotoxin challenge.
Measurements and main results: At 0, 120, and 240 mins, serum levels of TNF-alpha were measured using a specific rat TNF-alpha ELISA kit. U-74389G-treated endotoxemic animals showed significantly reduced TNF-alpha 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-alpha 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-alpha release during endotoxemia. Thus, 21-aminosteroids may lend themselves to evaluation in the treatment of septic states.