Thalidomide exerts its inhibitory action on tumor necrosis factor alpha by enhancing mRNA degradation.
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- A L Moreira
- Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
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- E P Sampaio
- Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
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- A Zmuidzinas
- Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
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- P Frindt
- Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
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- K A Smith
- Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
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- G Kaplan
- Laboratory of Cellular Physiology and Immunology, Rockefeller University, New York, New York 10021.
抄録
<jats:p>We have examined the mechanism of thalidomide inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production and found that the drug enhances the degradation of TNF-alpha mRNA. Thus, the half-life of the molecule was reduced from approximately 30 to approximately 17 min in the presence of 50 micrograms/ml of thalidomide. Inhibition of TNF-alpha production was selective, as other LPS-induced monocyte cytokines were unaffected. Pentoxifylline and dexamethasone, two other inhibitors of TNF-alpha production, are known to exert their effects by means of different mechanisms, suggesting that the three agents inhibit TNF-alpha 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-alpha production makes thalidomide an ideal candidate for the treatment of inflammatory conditions where TNF-alpha-induced toxicities are observed and where immunity must remain intact.</jats:p>
収録刊行物
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- The Journal of experimental medicine
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The Journal of experimental medicine 177 (6), 1675-1680, 1993-06-01
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1362544418750489984
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- NII論文ID
- 30017433610
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- ISSN
- 15409538
- 00221007
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