Key Point

Resveratrol, a substance found in red wine, has anti-inflammatory effects on lung tissue, making it a novel molecule for the possible treatment of COPD and asthma.

LONDON—Resveratrol, a substance found in red-skinned fruit, has been purported to have anti-inflammatory, antioxidative, and antiproliferative effects. It may be responsible for the health benefits ascribed to red wine consumption. New research has shown that resveratrol may act as an anti-inflammatory agent, making it useful in the treatment of COPD and corticosteroid-resistant asthma.¹

Louise Donnelly, PhD, and colleagues evaluated the effects of resveratrol and its cousin, quercetin, on inflammatory mediators such as interleukin 8 (IL-8), nitrates, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in A549 cells (derived from human lung carcinoma) and human airway epithelial cells. According to Dr. Donnelly, a Senior Lecturer in Thoracic Medicine at the National Heart and Lung Institute, Imperial College London, the findings show that “the discovery of a novel anti-inflammatory [agent] that is working under steroid-resistant conditions would be of benefit for [COPD and asthma] patients.”

MANY MEDIATORS AFFECTED

The investigators first looked at A549 cells. They found that resveratrol inhibited the release of GM-CSF from IL-1β–stimulated cells by about 75%. Quercetin inhibited the release of GM-CSF by about 50%, with less efficacy but similar potency than resveratrol. Both substances inhibited the release of IL-8 by about 40%. These effects can be a surrogate for the inhibition of inflammatory mediators in the lungs of patients afflicted with COPD or asthma.

It has been theorized that resveratrol is an estrogen agonist. However, Dr. Donnelly and her team do not believe that resveratrol’s anti-inflammatory effects come from its estrogen-like capabilities. Tamoxifen, an estrogen blocker, failed to antagonize the resveratrol-mediated inhibition of GM-CFS or IL-8 release from A549 cells. Similarly, the researchers do not believe that resveratrol acts as a glucocorticosteroid, although it is structurally similar to one. When mifepristone, a glucocorticosteroid receptor antagonist, was added to the resveratrol-treated A549 cells, the inhibition of IL-8 release was not affected. Dr. Donnelly acknowledges that the exact mechanisms behind resveratrol’s effects are not known, but she posited several theories. “It seems to be upstream of transcription factor activity, possibly acting as a kinase inhibitor. Alternatively, it may be acting as a ligand for one of the orphan nuclear receptors,” she explained.

Dr. Donnelly and her team also examined the effects of resveratrol on human airway epithelial cells treated with a “cytomix” containing 50 ng/ml of IL-1β, tumor necrosis factor-α, and interferon-γ. Cells treated with this mixture release inflammatory mediators. However, resveratrol dose dependently inhibited release of GM-CSF and IL-8 from these cells. Nitrate and nitrite release were also inhibited. Also noteworthy was that resveratrol (but not glucocorticosteroids) inhibited nitric-oxide synthase expression in this system.

WHAT DOES THIS MEAN FOR PATIENTS?

Can patients get relief with resveratrol? Dr. Donnelly said that issues with the agent’s bioavailability make administration difficult. “If it is ingested it is very unlikely that a large enough dose would reach the lungs,” she explained. The most plausible method for administering resveratrol would be through aerosolization, though this is years away. As for future research, Dr. Donnelly concluded, “We are trying to develop better molecules that do not have the bioavailabilty problems and also trying to understand the mechanism of action better.”

—Tamara Gibb

Reference
1. Donnelly LE, Newton R, Kennedy GE, et al. Anti-inflammatory effects of resveratrol in lung epithelial cells: molecular mechanisms. Am J Physiol Lung Cell Mol Physiol. 2004;287:L774-L783.

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