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.
Department of Medicine and Physical Therapy, University of Tokyo, Faculty of Medicine, Japan.
O
O
Kaminuma
A
A
Mori
M
M
Suko
Y
Y
Nishizaki
H
H
Kikkawa
K
K
Ikezawa
H
H
Okudaira
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