1996年10月
Interleukin-5 production by peripheral blood mononuclear cells of asthmatic patients is suppressed by T-440: Relation to phosphodiesterase inhibition
Journal of Pharmacology and Experimental Therapeutics
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- 巻
- 279
- 号
- 1
- 開始ページ
- 240
- 終了ページ
- 246
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
The effect of T-440, a selective type IV phosphodiesterase inhibitor, on cytokine production by peripheral blood mononuclear cells (PBMC) of atopic asthmatics was investigated. T-440 suppressed allergen-induced interleukin (IL)-5 production with a high potency (IC50 = 0.039 μg/ml) and allergen- induced proliferation of PBMC (IC50 = 0.30 μg/ml). T-440 also suppressed IL-2, IL-4 and IL-5 production by concanavalin A-activated PBMC in a concentration-dependent manner. The IC50 values for the suppression of cytokine synthesis were 0.11 μg/ml for IL-2, 0.57 μg/ml for IL-5 and 7.7 μg/ml for IL-4. cAMP-elevating agents, such as PGE2, forskolin and dibutyryl cAMP, suppressed IL-2, IL-4 and IL-5 production by concanavalin A- stimulated PBMC in a manner similar to that of T-440. T-440 inhibited cAMP- phosphodiesterase activity and raised the intracellular cAMP level of PBMC in a concentration-dependent manner, suggesting that the increase of intracellular cAMP caused by T-440 results in the reduction of cytokine production. We conclude that T-440 suppressed cytokine production by peripheral T lymphocytes via the protein kinase A pathway and may be an effective modality to treat atopic diseases associated with eosinophilic inflammation.
- リンク情報
- ID情報
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- ISSN : 0022-3565
- PubMed ID : 8858999
- SCOPUS ID : 0030425431