PDE4 inhibition and a corticosteroid in chronically antigen exposed conscious guinea-pigs

Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology
H Danahay, K J Broadley

Abstract

The physiological and pharmacological consequences of repeated aero-allergen challenge have not been previously characterized in conscious, sensitized guinea-pigs. This study was undertaken to compare the effects of two anti-inflammatory compounds, dexamethasone and Ro 20- 1724, on an acute and chronic airway inflammation, in terms of airway function, reactivity and leucocyte infiltration. Sensitized guinea-pigs received eight saline or ovalbumin (OvA) inhalation exposures over 4 weeks and either vehicle, the type 4 PDE inhibitor, Ro 20-1724 (3 mgkg(-1)), or dexamethasone (1.5 mg/kg(-1)), 30 min before and 6 h after each challenge. Airway function of the conscious animal (sGaw) was monitored over the duration of the first and final OvA challenge. Airway reactivity to the thromboxane mimetic, U46619, was also determined following the final OvA exposure as was the leucocyte infiltration. The first antigen challenge induced a large early (0-3h) and smaller late (17-24h) bronchoconstrictor response. Neither phase was affected by the drug treatments. The final OvA challenge induced early and late phase bronchoconstrictor responses but of similar magnitude. The late phase was also significantly prolonged. Ro 20-1724 and dexamethasone...Continue Reading

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Citations

Jun 1, 2005·Pharmacology & Therapeutics·María Jesús SanzEsteban J Morcillo
Sep 24, 2002·Pharmacology & Therapeutics·B J Nevin, K J Broadley
Mar 31, 2000·Current Opinion in Pulmonary Medicine·M S Barnette, D C Underwood
Jul 31, 2009·Bioorganic & Medicinal Chemistry Letters·Patrick LacombeRobert N Young
May 9, 2008·Pulmonary Pharmacology & Therapeutics·Brendan J Canning, Yangling Chou
Jan 22, 2008·Bioorganic & Medicinal Chemistry Letters·Michel GallantYves Girard
May 18, 2006·Journal of Mass Spectrometry : JMS·Kevin P BatemanDeborah Nicoll-Griffith
Mar 7, 2006·Bioorganic & Medicinal Chemistry Letters·Patrick LacombeYves Girard

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