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

1980; Elsevier BV; Volume: 66; Issue: 3 Linguagem: Inglês

10.1016/0091-6749(80)90040-8

1097-6825

George L. Martin, P ATKINS, Eliot H. Dunsky, Burton Zweiman,

Inhalation and Respiratory Drug Delivery

Eleven subjects demonstrating clinical, skin, and inhalation sensitivity to grass or ragweed pollen underwent 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 (PD2,, inhalation units increasing from 670 to ~3,280).Peak plasma histamine levels after antigen challenge decreased from II .4nglml to ~3.4 nglml during all drug administrations.Similarly, the percent increase in serum neutrophil chemotactic activity (NCA) also decreased, from 96% to 536% 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.Multiple host factors are thought to play a role in the pathogenesis of bronchial asthma.Based on findings from in vivo and in vitro studies, it has been postulated that pathogenetic mechanisms in this disease may include: (1) autonomic nervous system imbalance, l, * (2) hyperirritability of the bronchial tree,' and (3) local release of mediators of immediate hypersensitivity.3* 4 The in vivo effects of commonly used bronchodilators and corticosteroids on these pathogenetic mechanisms have not been well characterized.We have previously described increased neutrophil chemotactic activity (NCA) in sera of allergic subjects during bronchospasm induced by inhaled antigen.',6 In addition we and others have found increased plasma histamine levels after antigen-induced bronchospasm.7-s To further explore possible pathoge-