A NOVEL PHOSPHODIESTERASE INHIBITOR, T-440 - POSSIBLE MANAGEMENT OF EOSINOPHILIC INFLAMMATION BY DOWN-REGULATION OF INTERLEUKIN-5 PRODUCTION

The effect of T-440, a selective type IV phosphodiesterase (PDE IV) in hibitor, on interleukin (IL)-5 production by peripheral blood mononucl ear 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 co ncentration of 1 mu g/ml. T-440 inhibited cyclic AMP-phosphodiesterase (PDE) activity in a concentration-dependent manner and raised the int racellular cyclic AMP level of PBMCs significantly. Dibutyryl cyclic A MP suppressed IL-5 production by PBMCs in a similar way to T-440, sugg esting that the increase of intracellular cyclic AMP caused by T-440 r educes IL-5 production. T-440 may be an effective agent to treat atopi c diseases associated with eosinophilic inflammation, e.g. asthma and atopic dermatitis.