Theophylline's effect on neutrophil function and the late asthmatic response

Background: The decrement in lung function associated with the late asthmatic response after allergen challenge is believed to be mediated by an inflammatory response in the airways. Theophylline has been shown to inhibit the late asthmatic response, but the mechanisms are not clear. Objective: The study was designed to determine whether theophylline would inhibit the late asthmatic response by reducing neutrophil activation and subsequent superoxide production. Methods: Twelve subjects with asthma underwent treatment in this double-blind, randomized, crossover study. Each subject received theophylline and placebo in random order in two treatment periods of 3 weeks each. Each treatment period was followed by an allergen challenge and blood neutrophil function analysis. Results:At therapeutic levels theophylline increased FEV₁ at baseline and during the allergen challenge and increased the percentage suppression of neutrophil superoxide production by adenosine. Conclusion: Theophylline improved pulmonary function at baseline and during an allergen challenge, in part perhaps, by increasing the neutrophil's response to feedback inhibition by adenosine. However, theophylline did not decrease the severity and duration of the late asthmatic response.