Roflumilast inhibition of pulmonary leukotriene production and bronchoconstriction in ovalbumin-sensitized and -challenged Guinea pigs.
This study investigated the effects of roflumilast, a PDE4 inhibitor, on slow-reacting substance of anaphylaxis (SRS-A)-mediated bronchoconstriction and pulmonary leukotriene (LT) release in ovalbumin (OVA)-sensitized and -challenged guinea pigs. Animals were treated with roflumilast orally (0.04, 0.12, 0.4, or 4 mg/kg) or placebo 1 hour before OVA challenge. Bronchoconstriction was quantified by measuring airway conductance (Gaw) and dynamic lung compliance (Cdyn). Roflumilast significantly attenuated the decrease in Gaw (50% inhibitory dose [ID50] = 0.33 mg/kg) and Cdyn (ID50 = 0.25 mg/kg) in a dose-dependent manner and significantly inhibited Cys-LT (ID50 = 0.06 mg/kg) and LTB4 (ID50 = 0.05 mg/kg) release versus placebo-treated animals. Roflumilast did not affect LTD4-induced bronchoconstriction. These findings support the role of roflumilast as an anti-inflammatory treatment for asthma.
Wollin
Lutz
L
ALTANA Pharma, Konstanz, Germany. stefan-lutz.wollin@altanapharma.com
Marx
Degenhard
D
Wohlsen
Andrea
A
Beume
Rolf
R
D000485:Allergens / Q000009:adverse effects*; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000187:drug effects* / Q000276:immunology; D003521:Cyclopropanes / Q000494:pharmacology; D003545:Cysteine / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D006168:Guinea Pigs; D007975:Leukotriene B4 / Q000096:biosynthesis / Q000276:immunology; D015289:Leukotrienes / Q000096:biosynthesis / Q000276:immunology; D008297:Male; D010047:Ovalbumin / Q000009:adverse effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D013189:SRS-A / Q000096:biosynthesis / Q000276:immunology
D000485:Allergens; D000631:Aminopyridines; D001549:Benzamides; D003521:Cyclopropanes; D015289:Leukotrienes; D010726:Phosphodiesterase Inhibitors; D013189:SRS-A; C112381:cysteinyl-leukotriene; C424423:Roflumilast; D007975:Leukotriene B4; D010047:Ovalbumin; D003545:Cysteine