Inhibitory effects of theophylline, terbutaline, and hydrocortisone on leukotriene B4 and C4 generation by human leukocytes in vitro.

Leukotriene B4 (LTB4) and leukotriene C4 (LTC4) 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 LTB4 and LTC4 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 LTB4 and LTC4 content using reverse-phase high-performance liquid chromatography (HPLC). Total leukotriene (LT) production (the combined amounts of LTB4 and LTC4) was dose-dependently inhibited by pretreatment with theophylline, terbutaline or hydrocortisone. Therapeutic levels of hydrocortisone (5 x 10(-6) M) plus theophylline (5 x 10(-5) M) inhibited LTB4 and LTC4 production in an additive way, as did the combination of hydrocortisone plus terbutaline (5 x 10(-8) M). A statistically significant effect of diminished LTB4 generation was obtained after preincubation with therapeutic levels of theophylline plus terbutaline, but no such effect was seen for LTC4 levels. The in vitro inhibitory effects on LTB4 and LTC4 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.