IL-1-ALPHA, IL-6 AND TNF-ALPHA IN CUTANEOUS LESIONS OF LUPUS-ERYTHEMATOSUS ARE INHIBITED BY TOPICAL APPLICATION OF CALCIPOTRIOL

Lupus Erythematosus (LE) is an autoimmune disorder with an unknown eti ology and pathogenesis. Skin lesions of LE express several cytokines w hich correlate to histological findings such as IL-1 and IL-6 which ar e mediators of epidermal growth acid proliferation. Skin lesions of LE are generally treated with immunosuppressive agents such as oral or t opically applied corticosteroids. Recently a new drug, calcipotriol, a vitamin D3 analogue has been useful in treatment of psoriasis with no adverse effect on calcium metabolism. This drug shares immunomodulato ry effects with vit. D3 by inhibiting several cytokines produced by ke ratinocytes. In order to test the clinical effectiveness of calcipotri ol in cutaneous lesions of LE we have investigated several proinflamma tory cytokines such as: IL-1 alpha, IL-1 beta, IL-4, IL-5, IL-6, IL-8, MCP-1, TNF-alpha. Using an avidin-biotin immunoperoxidase system we h ave found IL-1 in both forms, IL-6 and TNF-alpha in basal keratinocyte s in patients affected with LE, after treatment they were reverted to normal. This inhibition is induced at a molecular level as demostrated by reduced IL-1, IL-6 and TNF alpha mRNA expression. This is the firs t report showing that calcipotriol is effective in cutaneous lesions o f LE and suggesting that this action is due to an inhibition of protei n synthesis and mRNA expression for IL-1 alpha, IL-6 and TNF alpha.