Etanercept decreases tumor necrosis factor-alpha activity in chronic wound fluid.
High levels of tumor necrosis factor-alpha (TNF-alpha), 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-alpha and has been shown to provide rapid and sustained improvement in rheumatoid arthritis by acting as a soluble receptor binding TNF-alpha and preventing its proinflammatory activities. Therefore, the aim of this study was to determine whether Etanercept could inhibit TNF-alpha activity in chronic wound fluid. Wound fluid was collected from the venous leg ulcers of 16 different patients. The effect of Etanercept on TNF-alpha activity was evaluated using both a TNF-alpha 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-alpha 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-alpha, which could reduce the chronicity of venous leg ulcers and thus aid in the healing of these wounds.
Cowin
Allison J
AJ
Child Health Research Institute, Women's and Children's Hospital, North Adelaide, SA, Australia. allison.cowin@adelaide.edu.au
Hatzirodos
Nicholas
N
Rigden
Justin
J
Fitridge
Robert
R
Belford
David A
DA
D000368:Aged; D000369:Aged, 80 and over; D001681:Biological Assay; D018929:Cell Culture Techniques; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D000068800:Etanercept; D005347:Fibroblasts / Q000187:drug effects*; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology*; D007155:Immunologic Factors / Q000494:pharmacology*; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism*; D014647:Varicose Ulcer / Q000378:metabolism*
D007074:Immunoglobulin G; D007155:Immunologic Factors; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept