The current therapies for skin inflammatory diseases have either significant risk of adverse effects associated with them, as in the case of corticosteroids, are ineffectual e.g. prostaglandin and leukotriene inhibitors, or target a single aspect of inflammation, e.g. vitamin D3 analogs. systemic inflammatory diseases are currently being targeted with anti-proinflammatory cytokine antibodies and receptor/ binding proteins. Tumor necrosis factor alpha (TNF) has attracted much attention and encouraging studies have been reported in the treatment of rheumatoid arthritis, inflammatory bowel disease and metastatic Crohn's disease. Unfortunately, these therapies are not suited to treating skin diseases due to problems inherent in the delivery of large molecules through the stratum corneum of the skin, the very large doses required for systemic delivery, and cost-effectiveness. Elevated levels of TNP have been recently found in psoriatic plagues and there is reason to believe that TNT is involved also in atopic dermatitis and allergic contact dermatitis. This proposal is aimed at identifying small drugs that are being marketed for non-inflammatory uses and which potently inhibit TNF expression in inflammatory cells and epidermis and suppress swelling and TNF expression in mouse models of skin inflammatory diseases.National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
