Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease.
Culpitt SV., de Matos C., Russell RE., Donnelly LE., Rogers DF., Barnes PJ.
Chronic obstructive pulmonary disease (COPD) is characterized by a neutrophilic airway inflammation that can be demonstrated by examination of induced sputum. Theophylline has antiinflammatory effects in asthma, and in the present study we investigated whether a similar effect occurs in COPD patients treated with low doses of theophylline. Twenty-five patients with COPD were treated with theophylline (plasma level of 9-11 mg/L) for 4 weeks in a placebo-controlled, randomized, double-blind crossover study. Theophylline was well tolerated. Induced sputum inflammatory cells, neutrophils, interleukin-8, myeloperoxidase, and lactoferrin were all significantly reduced by about 22% by theophylline. Neutrophils from subjects treated with theophylline showed reduced chemotaxis to N-formyl-met-leu-phe (approximately 28%) and interleukin-8 (approximately 60%). Neutrophils from a healthy donor showed reduced chemotaxis (approximately 30%) to induced sputum samples obtained during theophylline treatment. These results suggest that theophylline has antiinflammatory properties that may be useful in the long-term treatment of COPD.