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The effect of selective phosphodiesterase 3 and 4 isoenzyme inhibitors and established anti‐asthma drugs on inflammatory cell activation
Author(s) -
Banner K.H.,
Moriggi E.,
Ros B.,
Schioppacassi G.,
Semeraro C.,
Page C.P.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16030.x
Subject(s) - histamine , rolipram , pharmacology , leukotriene b4 , superoxide , chemistry , mast cell , eosinophil , zymosan , leukotriene , immunology , endocrinology , phosphodiesterase , inflammation , medicine , biochemistry , in vitro , enzyme , asthma
1 This study aimed to evaluate the effects of phosphodiesterase (PDE) inhibitors and currently prescribed anti‐asthma drugs for their ability to inhibit inflammatory cell activation in vitro . 2 Alveolar macrophages and eosinophils were isolated from the bronchoalveolar lavage (BAL) fluid of ovalbumin (Ovalb)‐sensitized guinea‐pigs. Opsonized zymosan (OZ) and PAF stimulated leukotriene B 4 (LTB 4 ) release from eosinophils was measured by radioimmunoassay. Ovalb‐induced superoxide generation was measured by reduction of cytochrome C. 3 Monocytes were separated from human peripheral venous blood and mast cells were dispersed from human lung fragments. Lipopolysaccharide (LPS)‐induced tumour necrosis factor‐α (TNF‐α) release from monocytes was measured by ELISA and anti‐IgE stimulated histamine release from mast cells was measured by a radioenzymatic method. 4 The β 2 agonist, salbutamol inhibited TNF‐α release from monocytes and histamine release from mast cells whilst having no effect on eosinophil‐derived LTB 4 release or macrophage superoxide generation. 5 The PDE 3 inhibitor, milrinone produced a concentration‐related inhibition of TNF‐α release from monocytes which achieved statistical significance at 10 −5 m but inhibited LTB 4 release from eosinophils and superoxide generation from macrophages only at the highest concentration (10 −3 m ) examined. Milrinone had no effect on histamine release from mast cells. 6 The selective PDE 4 inhibitors, denbufylline and rolipram and the corticosteroid, beclomethasone produced a concentration‐related inhibition of LTB 4 release from eosinophils, TNF‐α release from monocytes and superoxide generation from alveolar macrophages whilst having no effect on histamine release from mast cells. 7 The mixed PDE 3/4 inhibitor, benzafentrine produced a concentration‐related inhibition of LTB 4 release from eosinophils, TNF‐α release from monocytes, superoxide generation from alveolar macrophages and histamine release from mast cells. 8 In conclusion these data clearly show that both established anti‐asthma medication as well as PDE inhibitors have the potential to inhibit inflammatory cell activation in vitro but that the anti‐secretory actions of β 2 agonists, corticosteroids and PDE inhibitors are distinct.