1998 Volume 21 Issue 6 Pages 638-640
We investigated the in vivo effects of thalidomide on the production of tumor necrosis factor-α(TNF-α). An in vivo systemic release of TNF-αoccurred after the injection of lipopolysaccharide (LPS) in male ddY mice, and the TNF-α serum levels reached 652.2±75.7 pg/ml 90 min after the injection of LPS (0.3 mg/kg, i. p.). When thalidomide (1, 3, or 6 mg/kg) was administered intraperitoneally 3h before the injection of LPS (0.3 mg/kg, i.p.), thalidomide markedly enhanced LPS-induced TNF-α release in a dose-dependent manner. The TNF-α serum levels at 90 min were 640±58.6, 1985±132.6, and 2795±203.5 pg/ml, respcetively, compared to 628.6±64.4 pg/ml in mice treated with LPS-alone. Pretreatment with a single injection of thalidomide (1, 3, or 6 mg/kg. i. p.) dosedependently increased the subsequent mortality caused by a challenge with LPS (15 mg/kg, i. p.), a dose that caused death in 10% of the control mice. We conclude that thalidomide enhances in vivo TNF-α secretion and the lethality of LPS in mice.