Long-term treatment with theophylline reduces neutrophils, interleukin-8 and tumor necrosis factor-alpha in the sputum of patients with chronic obstructive pulmonary disease.
BACKGROUND
The non-selective phosphodiesterase inhibitor theophylline has bronchodilator/anti-inflammatory properties and is widely used in the treatment of airways diseases. We determined the effect of long-term theophylline treatment on airway inflammation in patients with chronic obstructive pulmonary disease (COPD).


METHODS
Seventeen stable COPD patients were enrolled in the 12-month study. Theophylline was administered at 400mg/day. We studied changes in symptoms, spirometry, sputum volume, and sputum inflammatory cytokines levels. We also examined the effects of theophylline on the release of inflammatory cytokines in vitro by measuring interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha levels from lipopolysaccharide (LPS)-stimulated neutrophils and THP-1 cells.


RESULTS
Forced vital capacity was increased and sputum IL-8 levels decreased after 4 weeks of theophylline treatment. After 6 months of theophylline treatment, forced expiratory volume in 1s was increased, and neutrophils counts and TNF-alpha levels in sputum were reduced. Levels of IL-8 and TNF-alpha released by LPS-stimulated THP-1 cells were reduced by treatment with theophylline at 10microg/ml. In contrast, IL-8 levels released by LPS-stimulated neutrophils were reduced by treatment with theophylline at 100microg/ml.


CONCLUSIONS
Our clinical study of small population showed that long-term treatment with theophylline seems to reduce airway inflammation in stable COPD patients.
Iiboshi
Hirotoshi
H
The Third Department of Internal Medicine, Miyazaki Medical College, Miyazaki University School of Medicine, Kihara 5200, Miyazaki 889-1692, Japan.
Ashitani
Jun-Ichi
J
Katoh
Shigeki
S
Sano
Arisa
A
Matsumoto
Nobuhiro
N
Mukae
Hiroshi
H
Nakazato
Masamitsu
M
D000284:Administration, Oral; D000368:Aged; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D004334:Drug Administration Schedule; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D012720:Severity of Illness Index; D013147:Spirometry; D013183:Sputum / Q000187:drug effects* / Q000378:metabolism; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D001993:Bronchodilator Agents; D016209:Interleukin-8; D008070:Lipopolysaccharides; D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D013806:Theophylline