Thalidomide Exerts Its Inhibitory Action on Tumor

We have examined the mechanism of thalidomide inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor ot (TNF<~) production and found that the drug enhances the degradation of TNF-oe mRNA. Thus, the half-life of the molecule was reduced from "o30 to ~o17 rain in the presence of 50/zg/ml of thalidomide. Inhibition of TNF-ot production was selective, as other LPS-induced monocyte cytokines were unaffected. PentoxifyUine and dexamethasone, two other inhibitors of TNF-c~ production, are known to exert their effects by means of different mechanisms, suggesting that the three agents inhibit TNF-c~ synthesis at distinct points of the cytokine biosynthetic pathway. These observations provide an explanation for the synergistic effects of these drugs. The selective inhibition of TNF-cr production makes thalidomide an ideal candidate for the treatment of inflammatory conditions where TNF-c~-induced toxicities are observed and where immunity must remain intact.