The role of theophylline and phosphodiesterase4 isoenzyme inhibitors as anti-inflammatory drugs.
Theophylline has been used for over a century in the treatment of asthma and while it is used principally as a bronchodilator, a number of recent studies have demonstrated potential anti-inflammatory and immunomodulatory activity. Indeed, regular treatment with low-dose theophylline, affords significant clinical benefit at the expense of unwanted side-effects associated with this drug, including headache and vomiting. The mechanism of action of theophylline is unclear, although a significant body of evidence points to an involvement of phosphodiesterase enzyme inhibition. Phosphodiesterases are a diverse group of enzymes that belong to at least seven families and of particular interest is the role of phosphodiesterase 4 isoenzyme as it is distributed in a number of inflammatory and immune cells and whose inhibition results in the downregulation of inflammatory and immune cell function. The discovery of pharmacological drugs selective for this isoenzyme has been viewed with interest in light of the positive results from preclinical and early clinical studies. Whether orally active safe phosphodiesterase 4 isoenzyme inhibitors will be useful in the treatment of asthma remains to be established.
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The Sackler Institute of Pulmonary Pharmacology, The Department of Respiratory Medicine, Kings College School of Medicine and Dentistry, London, UK.
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D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy*; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D003876:Dermatitis, Atopic / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D018655:Lymphocyte Count; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology; D013806:Theophylline / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4