Etanercept decreases tumor necrosis factor-alpha activity in chronic wound fluid

The definitive version is available at www.blackwell-synergy.comHigh levels of tumor necrosis factor-α (TNF-α), a pro-inflammatory cytokine, are present in the wound fluid of chronic nonhealing wounds. This leads to increased inflammation, cytokine expression, and ultimately results in impaired wound healing and tissue destruction. Etanercept is a recombinant fusion protein that consists of the soluble TNF receptor (p75) linked to the Fc portion of human IgG1. It is an effective inhibitor of TNF-α and has been shown to provide rapid and sustained improvement in rheumatoid arthritis by acting as a soluble receptor binding TNF-α and preventing its proinflammatory activities. Therefore, the aim of this study was to determine whether Etanercept could inhibit TNF-α activity in chronic wound fluid. Wound fluid was collected from the venous leg ulcers of 16 different patients. The effect of Etanercept on TNF-α activity was evaluated using both a TNF-α bioassay and an enzyme-linked immunoassay. Etanercept was found to reduce the cytotoxic effect of chronic wound fluid on L929 fibroblasts by approximately 30% and neutralized TNF-α binding in the enzyme-linked immunoassay by up to 80%. Direct application of Etanercept to chronic wounds may therefore reduce the inflammatory activity of TNF-α, which could reduce the chronicity of venous leg ulcers and thus aid in the healing of these wounds.Allison J. Cowin, Nicholas Hatzirodos, Justin Rigden, Robert Fitridge and David A. Belfor