Effects of theophylline, terbutaline, and prednisone on antigen-induced bronchospasm and mediator release

Eleven subjects demonstrating clinical, skin, and inhalation sensitivity to grass or ragweed pollen underwnet serial inhalation challenges, with and without orally administered theophylline, terbutaline, and prednisone. Comparisons of antigen sensitivity and mediator release were made during these challenges. All three drugs significantly reduced antigen sensitivity (PD20 inhalation units increasing from 670 to greater than or equal to 3,280). Peak plasma histamine levels after antigen challenge decreased from 11.4 ng/ml to less than or equal to 3.4 ng/ml during all drug administrations. Similarly, the percent increase in serum neutrophil chemotactic activity (NCA) also decreased, from 96% to less than or equal to 36% during drug administrations. However, even at antigen doses resulting in bronchospasm during drug administration the systemic appearance of NCA and histamine were reduced. We conclude that prednisone, theophylline, and terbutaline significantly reduce antigen-induced bronchospasm and mediator release. The occurrence of bronchospasm despite the inhibition of histamine and NCA suggests either that the local concentration of these mediators are critical or that other mediators produce the bronchospasm observed.