THALIDOMIDE PROMOTES THE RELEASE OF TUMOR-NECROSIS-FACTOR-ALPHA (TNF-ALPHA) AND LETHALITY BY LIPOPOLYSACCHARIDE IN MICE

We investigated the in vivo effects of thalidomide on the production o f tumor necrosis factor-alpha (TNF-alpha). An in viva systemic release of TNF-alpha occurred after the injection of lipopolysaccharide (LPS) in male ddY mice, and the TNF-a serum levels reached 652,2+/-75.7pg/m l 90 min after the injection of LPS (0.3 mg/kg, i. p.). When thalidomi de (1, 3, or 6 mg/kg) was administered intraperitoneally 3 h before th e injection of LPS (0.3 mg/kg, i. p.), thalidomide markedly enhanced L PS-induced TNF-a: release in a dose-dependent manner. The TNF-alpha se rum levels at 90 min were 640+/-58.6, 1985+/-132.6, and 2795+/-203.5 p g/ml, respectively, compared to 628.6+/-64.4 pg/ml in mice treated Kit h LPS-alone, Pretreatment with a single injection of thalidomide (1, 3 , or 6 mg/kg, i. p,) dose-dependently increased the subsequent mortali ty caused by a challenge with LPS (15 mg/kg, i. p.), a dose that cause d death in 10% of the control mice. We conclude that thalidomide enhan ces in vivo TNF-alpha secretion and the lethality of LPS in mice.