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 of tumor necrosis factor-alpha (TNF-alpha). An in vivo systemic release of TNF-alpha occurred after the injection of lipopolysaccharide (LPS) in male ddY mice, and the TNF-alpha 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 3 h before the injection of LPS (0.3 mg/kg, i. p.), thalidomide markedly enhanced LPS-induced TNF-alpha release in a dose-dependent manner. The TNF-alpha serum levels at 90 min were 640 +/- 58.6, 1985 +/- 132.6, and 2795 +/- 203.5 pg/ml, respectively, 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.) dose-dependently 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-alpha secretion and the lethality of LPS in mice.
Ishikawa
M
M
Department of Pharmacology and Toxicology, Tohoku College of Pharmacy, Sendai, Japan.
Kanno
S
S
Takayanagi
M
M
Takayanagi
Y
Y
Sasaki
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000633:toxicity*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D013792:Thalidomide / Q000633:toxicity*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide