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Inhibitory effects of theophylline, terbutaline, and hydrocortisone on leukotriene B 4 and C 4 generation by human leukocytes in vitro
Author(s) -
Shimizu T.,
Kristjánsson S.,
Wennergren G.,
Hansson G. C.,
Strandvik B.
Publication year - 1994
Publication title -
pediatric pulmonology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.866
H-Index - 106
eISSN - 1099-0496
pISSN - 8755-6863
DOI - 10.1002/ppul.1950180302
Subject(s) - theophylline , terbutaline , medicine , bronchodilator , in vitro , leukotriene , hydrocortisone , pharmacology , leukotriene c4 , leukotriene b4 , asthma , endocrinology , inflammation , biochemistry , chemistry
Leukotriene B 4 (LTB 4 ) and leukotriene C 4 (LTC 4 ) are considered to be important mediators in the pathophysiology of asthma. Theophylline, terbutaline, and hydrocortisone are drugs commonly used in the treatment of asthma. In the present study we have investigated the in vitro inhibitory effects of theophylline, terbutaline, and hydrocortisone on LTB 4 and LTC 4 generation from human leukocytes. After preincubation in the presence of these drugs, the cells were stimulated with the calcium ionophore A 23187 and the supernatants were analyzed for their LTB, and LTC, content using reverse‐phase high‐performance liquid chromatography (HPLC). Total leukotriene (LT) production (the combined amounts of LTB 4 and LTC 4 ) was dose‐dependently inhibited by pretreatment with theophylline, terbutaline or hydrocortisone. Therapeutic levels of hydrocortisone (5 × 10 −6 M) plus theophylline (5 × 10 −5 M) inhibited LTB 4 and LTC 4 production in an additive way, as did the combination of hydrocortisone plus terbutaline (5 × 10 −8 M). A statistically significant effect of diminished LTB, generation was obtained after preincubation with therapeutic levels of theophylline plus terbutaline, but no such effect was seen for LTC 4 levels. The in vitro inhibitory effects on LTB 4 and LTC 4 generation from human leukocytes by theophylline, terbutaline, and hydrocortisone, as well as the additive effect of hydrocortisone plus theophylline or terbutaline, add to our understanding of the therapeutic effects of these drugs in the treatment of bronchopulmonary obstruction. Pediatr Pulmonol. 1994;18:129–134. © 1994 Wiley‐Liss, Inc.