Roflumilast inhibition of pulmonary leukotriene production and bronchoconstriction in ovalbumin-sensitized and -challenged guinea pigs

被引:12
作者
Wollin, L [1 ]
Marx, D [1 ]
Wohlsen, A [1 ]
Beume, R [1 ]
机构
[1] ALTANA Pharma AG, D-78467 Constance, Germany
关键词
phosphodiesterase; 4; inhibitor; slow-reacting substance of anaphylaxis (SRS-A); leukotriene; asthma; guinea pig;
D O I
10.1080/02770900500370858
中图分类号
R392 [医学免疫学];
学科分类号
100102 [免疫学];
摘要
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 (ID 50 = 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.
引用
收藏
页码:873 / 878
页数:6
相关论文
共 22 条
[1]
MECHANICS OF RESPIRATION IN UNANESTHETIZED GUINEA PIGS [J].
AMDUR, MO ;
MEAD, J .
AMERICAN JOURNAL OF PHYSIOLOGY, 1958, 192 (02) :364-368
[2]
AN INVIVO MODEL FOR MEASURING ANTIGEN-INDUCED SRS-A-MEDIATED BRONCHOCONSTRICTION AND PLASMA SRS-A LEVELS IN THE GUINEA-PIG [J].
ANDERSON, WH ;
ODONNELL, M ;
SIMKO, BA ;
WELTON, AF .
BRITISH JOURNAL OF PHARMACOLOGY, 1983, 78 (01) :67-74
[3]
Aoki M, 2001, J PHARMACOL EXP THER, V297, P165
[4]
Leukotriene B4 mediates histamine induction of NF-κB and IL-8 in human bronchial epithelial cells [J].
Aoki, Y ;
Qiu, DM ;
Zhao, GH ;
Kao, PN .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 1998, 274 (06) :L1030-L1039
[5]
BARDIN PG, 2005, ANN ASTHMA ALLERGY I, V94, P107
[6]
BATEMAN ED, 2005, ANN ALLERG ASTHMA IM, V94, P169
[7]
LEUKOTRIENE B-4 TRANSCRIPTIONALLY ACTIVATES INTERLEUKIN-6 EXPRESSION INVOLVING NK-CHI-B AND NF-IL6 [J].
BRACH, MA ;
DEVOS, S ;
ARNOLD, C ;
GRUSS, HJ ;
MERTELSMANN, R ;
HERRMANN, F .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1992, 22 (10) :2705-2711
[8]
Bundschuh DS, 2001, J PHARMACOL EXP THER, V297, P280
[9]
Pharmacology of airway inflammation in asthma and COPD [J].
Caramori, G ;
Adcock, I .
PULMONARY PHARMACOLOGY & THERAPEUTICS, 2003, 16 (05) :247-277
[10]
Differences in airway inflammation in patients with fixed airflow obstruction due to asthma or chronic obstructive pulmonary disease [J].
Fabbri, LM ;
Romagnoli, M ;
Corbetta, L ;
Casoni, G ;
Busljetic, K ;
Turato, G ;
Ligabue, G ;
Ciaccia, A ;
Saetta, M ;
Papi, A .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 167 (03) :418-424