一种新型磷酸二酯酶抑制剂T-440：通过下调白细胞介素-5的产生来控制嗜酸性粒细胞炎症的可能性。

A novel phosphodiesterase inhibitor, T-440: possible management of eosinophilic inflammation by down-regulation of interleukin-5 production.

作者信息

Kaminuma O, Mori A, Suko M, Nishizaki Y, Kikkawa H, Ikezawa K, Okudaira H

机构信息

Department of Medicine and Physical Therapy, University of Tokyo, Faculty of Medicine, Japan.

出版信息

Int Arch Allergy Immunol. 1996;111 Suppl 1:16-8. doi: 10.1159/000237407.

DOI:10.1159/000237407

PMID:8906105

Abstract

The effect of T-440, a selective type IV phosphodiesterase (PDE IV) inhibitor on interleukin (IL)-5 production by peripheral blood mononuclear cells (PBMCs) of atopic asthmatic subjects was investigated. PBMCs produced IL 5 following challenge with specific allergen in vitro. T-440 suppressed allergen-induced IL-5 production significantly at a concentration of 1 microgram/ml. T-440 inhibited cyclic AMP-phosphodiesterase (PDE) activity in a concentration dependent manner and raised the intracellular cyclic AMP level of PBMCs significantly. Dibutyryl cyclic AMP suppressed IL-5 production by PBMCs in a similar way to T-440, suggesting that the increase of intracellular cyclic AMP caused by T-440 reduces IL-5 production. T-440 may be an effective agent to treat atopic diseases associated with eosinophilic inflammation, e.g. asthma and atopic dermatitis.

摘要

研究了选择性IV型磷酸二酯酶（PDE IV）抑制剂T-440对特应性哮喘患者外周血单个核细胞（PBMC）产生白细胞介素（IL）-5的影响。体外特定变应原刺激后，PBMC产生IL-5。T-440在浓度为1微克/毫升时能显著抑制变应原诱导的IL-5产生。T-440以浓度依赖性方式抑制环磷酸腺苷磷酸二酯酶（PDE）活性，并显著提高PBMC的细胞内环磷酸腺苷水平。二丁酰环磷酸腺苷以与T-440相似的方式抑制PBMC产生IL-5，这表明T-440引起的细胞内环磷酸腺苷增加会减少IL-5的产生。T-440可能是治疗与嗜酸性粒细胞炎症相关的特应性疾病（如哮喘和特应性皮炎）的有效药物。