THALIDOMIDE DECREASES THE PRODUCTION OF GM-CSF AND TNF-ALPHA IN THE MIXED EPIDERMAL CELL-LYMPHOCYTE REACTION

Thalidomide is an effective treatment for several dermatological disea ses. Recently, it has been used to treat Langerhans cell histiocytosis . The mechanism of this effect is poorly understood. In order to try t o define the mechanism of action of thalidomide, we studied its effect s (26 to 2,600 ng/ml) on lymphocyte proliferation in mixed allogeneic reactions, on the induction of allogeneic cytotoxic activity, and on t he production of several cytokines in the mixed epidermal cell-lymphoc yte reaction, using an ELISA or a RIA test. Thalidomide and its solvan t had no effect on either lymphocyte proliferation or the cytotoxic ac tivity induced in mixed allogeneic reactions. In mixed epidermal cell- lymphocyte reactions, the production of GM-CSF was decreased when eith er lymphoid cells or epidermal cells (EC) were preincubated with thali domide. The production of TNF-alpha and IL-6 was decreased only when l ymphoid cells were preincubated with thalidomine. The production of IL -1 beta was not decreased when either EC or lymphoid cells were preinc ubated with thalidomide. In conclusion, thalidomide decreases the prod uction of several cytokines in MECLR, especially GM-CSF and TNF-alpha, which play a major role in the viability and function of Langerhans c ells. This effect of thalidomide on the lymphocyte-epidermal cell inte ractions may, at least partly, explain the effect of thalidomide on La ngerhans cell histiocytosis.