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) 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.
Kaminuma
O
O
Department of Medicine and Physical Therapy, University of Tokyo, Faculty of Medicine, Japan.
Mori
A
A
Suko
M
M
Nishizaki
Y
Y
Kikkawa
H
H
Ikezawa
K
K
Okudaira
H
H
D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000485:Allergens; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001249:Asthma / Q000188:drug therapy; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D015536:Down-Regulation; D004804:Eosinophils / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D015848:Interleukin-5 / Q000096:biosynthesis*; D008925:Mites / Q000276:immunology; D009281:Naphthalenes / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism*; D011728:Pyridones / Q000494:pharmacology*
D000485:Allergens; D000893:Anti-Inflammatory Agents; D015848:Interleukin-5; D009281:Naphthalenes; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; C101791:T 440; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4