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

1999; Lippincott Williams & Wilkins; Volume: 27; Issue: 6 Linguagem: Inglês

10.1097/00003246-199906000-00044

1530-0293

Christine Lehmann, Karl Egerer, Alexander Georgiew, Mathias Weber, Tilman Grune, Wolfgang J. Kox,

Neuropeptides and Animal Physiology

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. (Crit Care Med 1999; 27:1164-1167)