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

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.
AuthorsO Kaminuma, A Mori, M Suko, Y Nishizaki, H Kikkawa, K Ikezawa, H Okudaira
JournalInternational archives of allergy and immunology (Int Arch Allergy Immunol) Vol. 111 Suppl 1 Pg. 16-8 ( 1996) ISSN: 1018-2438 [Print] Switzerland
PMID8906105 (Publication Type: Journal Article)
Chemical References
  • Allergens
  • Anti-Inflammatory Agents
  • Interleukin-5
  • Naphthalenes
  • Phosphodiesterase Inhibitors
  • Pyridones
  • T 440
  • Cyclic AMP
  • Phosphoric Diester Hydrolases
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4
Topics
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Allergens
  • Animals
  • Anti-Inflammatory Agents (pharmacology)
  • Asthma (drug therapy)
  • CD4-Positive T-Lymphocytes (metabolism)
  • Cyclic AMP (metabolism)
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Down-Regulation
  • Eosinophils (immunology)
  • Humans
  • Hypersensitivity (immunology)
  • Interleukin-5 (biosynthesis)
  • Mites (immunology)
  • Naphthalenes (pharmacology)
  • Phosphodiesterase Inhibitors (pharmacology)
  • Phosphoric Diester Hydrolases (metabolism)
  • Pyridones (pharmacology)

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