Inhibition by red wine extract, resveratrol, of cytokine release by alveolar macrophages in COPD

Abstract

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.

Characterization of cigarette smoke-induced inflammatory and mucus hypersecretory changes in rat lung and the role of CXCR2 ligands in mediating this effect

“…The second wave of CINC-2 production, which coincides with the greatest levels of CINC-1 and neutrophils in the lung, may act in a comparable fashion to that hypothesized for CINC-1. These results are similar to clinical observations indicating the excessive neutrophilia observed in the airways of COPD patients may be due in part to the overproduction of neutrophil chemoattractants, like IL-8 and GRO-␣, by resident tissue cells like alveolar macrophages or epithelial cells (4,23). IL-8 and GRO-␣ are found at elevated levels in the induced sputum of COPD patients compared with healthy smokers (14,29).…”

“…CS induced dose-dependent effects on neutrophil chemokine production and neutrophil infiltration into the lung and airway lumen. This could suggest that CS induces the local production of CXCR2 ligands (IL-8 and GRO-␣ homologs) from epithelial cells and/or alveolar macrophages, which would then serve to recruit neutrophils into the airways (4,23). CS also induced dose-dependent increases in goblet cell formation and mucin secretory capacity of rat airways.…”

“…Additional mediators are also likely to contribute to the neutrophil infiltration such as leukotriene B 4 , matrix fragments, and C5a, thus inhibition of the CXCR2 receptor may serve to dampen the inflammation rather than completely abolish it.…”

Dietary factors and lung function in the general population: wine and resveratrol intake

“…A putative candidate that may account for the observed beneficial effect of wine is resveratrol, a polyphenol present in the skin of grapes. Resveratrol possesses antiinflammatory properties in airway epithelial cells [10] and alveolar macrophages derived from COPD patients [11]. The mechanism of this action may be explained by the resveratrol-mediated induction of Sirtuin (SIRT)1 activity [12,13].…”

Anti-atherogenic effects of resveratrol

“…Cultured murine macrophages, after treatment with RS, have been shown to reduce gene expression, synthesis and secretion of interleukin-6 (Zhong et al, 1999). The inflammatory process was found to be suppressed by RS, through mediating various inflammatory markers such as inhibition of secretion of interleukin-8 and granulocyte macrophage colony-stimulating factors (Culpitt et al, 2003;Donnelly et al, 2004), endothelial-leukocyte adhesion molecules, vascular cell adhesion molecule-1, and by inhibiting the secretion of histamine and tumor necrosis factor-a (Carluccio et al, 2003).…”