Bronchodilators modulate inflammation in chronic obstructive pulmonary disease subjects

• Published in: Pharmacological research Vol. 66; no. 4; pp. 343 - 348
• Main Authors: Santus, Pierachille, Buccellati, Carola, Centanni, Stefano, Fumagalli, Francesca, Busatto, Paolo, Blasi, Francesco, Sala, Angelo
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.10.2012
• Subjects: Aged; Aged, 80 and over; Bronchodilator Agents - pharmacology; Bronchodilator Agents - therapeutic use; Bronchodilators; Chronic obstructive pulmonary disease; Ethanolamines - pharmacology; Ethanolamines - therapeutic use; Female; Formoterol Fumarate; Humans; Leukotriene B4; Leukotriene B4 - immunology; Lung - drug effects; Lung - immunology; Male; Neutrophils; Neutrophils - drug effects; Neutrophils - immunology; Pulmonary Disease, Chronic Obstructive - drug therapy; Pulmonary Disease, Chronic Obstructive - immunology; Scopolamine Derivatives - pharmacology; Scopolamine Derivatives - therapeutic use; Superoxide anion production; Superoxides - immunology; Tiotropium Bromide; Bronchodilators; Chronic obstructive pulmonary disease; Leukotriene B4; Superoxide anion production; Neutrophils
• ISSN: 1043-6618; 1096-1186
• DOI: 10.1016/j.phrs.2012.05.007

Chronic obstructive pulmonary disease (COPD) is characterized by neutrophilic airway inflammation and oxidative stress. Leukotriene B4 (LTB4), a potent proinflammatory mediator, is synthesized by 5-lipoxygenase (5-LO), which is activated by the presence of lipid hydroperoxides resulting from oxidative stress on biological membranes. We proposed to evaluate the effect of a four week treatment with two different bronchodilators of common practice in COPD treatment, on the production of reactive oxygen species (ROS), in particular superoxide anions, and of LTB4 by peripheral blood neutrophils obtained from COPD subjects. 24 subjects among the COPD outpatients were enrolled, and randomized to receive either formoterol (12μg bid) or tiotropium (18μg od). Peripheral blood neutrophils were obtained at the start and at the end of the treatment, and production of superoxide anions and of LTB4 were evaluated as previously published. The results obtained showed a decrease in the unstimulated production of superoxide by isolated neutrophils in both groups, but tiotropium only was effective in modulating the production of LTB4, while formoterol caused an increased production of superoxide in response to fMLP, when compared to values obtained before treatment. In conclusion, tiotropium showed a better antiinflammatory activity profile when compared to formoterol in a clinical setting, reducing superoxide and LTB4 production by peripheral neutrophils obtained from COPD subjects.