Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease.
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.
Culpitt
Sarah V
SV
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London, United Kingdom. duncan.rogers@ic.ac.uk
de Matos
Carmen
C
Russell
Richard E
RE
Donnelly
Louise E
LE
Rogers
Duncan F
DF
Barnes
Peter J
PJ
D000368:Aged; D002634:Chemotaxis, Leukocyte / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils; D011336:Probability; D029424:Pulmonary Disease, Chronic Obstructive / Q000175:diagnosis / Q000188:drug therapy*; D012016:Reference Values; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D013147:Spirometry; D013183:Sputum / Q000166:cytology*; D018709:Statistics, Nonparametric; D013806:Theophylline / Q000008:administration & dosage*
D013806:Theophylline