CHRONIC OBSTRUCTIVE PULMONARY DISEASE Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD

Background: The pathophysiology of chronic obstructive pulmonary disease (COPD) features pulmonary inflammation with a predominant alveolar macrophage involvement. Bronchoalveolar macrophages from patients with COPD release increased amounts of inflammatory cytokines in vitro, an effect that is not inhibited by the glucocorticosteroid dexamethasone. Resveratrol (3,5,49-trihydroxystilbene) is a component of red wine extract that has anti-inflammatory and antioxidant properties. A study was undertaken to determine whether or not resveratrol would inhibit cytokine release in vitro by alveolar macrophages from patients with COPD. Methods: Alveolar macrophages were isolated from bronchoalveolar lavage (BAL) fluid from cigarette smokers and from patients with COPD (n = 15 per group). The macrophages were stimulated with either interleukin (IL)-1b or cigarette smoke media (CSM) to release IL-8 and granulocyte macrophage-colony stimulating factor (GM-CSF). The effect of resveratrol was examined on both basal and stimulated cytokine release. Results: Resveratrol inhibited basal release of IL-8 in smokers and patients with COPD by 94% and 88% respectively, and inhibited GM-CSF release by 79% and 76% respectively. Resveratrol also inhibited stimulated cytokine release. Resveratrol reduced IL-1b stimulated IL-8 and GM-CSF release in both smokers and COPD patients to below basal levels. In addition, resveratrol inhibited CSM stimulated IL-8 release by 61% and 51% respectively in smokers and COPD patients, and inhibited GM-CSF release by 49% for both subject groups. Conclusions: Resveratrol inhibits inflammatory cytokine release from alveolar macrophages in COPD. Resveratrol or similar compounds may be effective pharmacotherapy for macrophage pathophysiology in COPD.