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 diseases. Recently, it has been used to treat Langerhans cell histiocytosis. The mechanism of this effect is poorly understood. In order to try to define the mechanism of action of thalidomide, we studied its effects (26 to 2,600 ng/ml) on lymphocyte proliferation in mixed allogeneic reactions, on the induction of allogeneic cytotoxic activity, and on the production of several cytokines in the mixed epidermal cell-lymphocyte reaction, using an ELISA or a RIA test. Thalidomide and its solvant had no effect on either lymphocyte proliferation or the cytotoxic activity induced in mixed allogeneic reactions. In mixed epidermal cell-lymphocyte reactions, the production of GM-CSF was decreased when either lymphoid cells or epidermal cells (EC) were preincubated with thalidomide. The production of TNF-alpha and IL-6 was decreased only when lymphoid cells were preincubated with thalidomine. The production of IL-1 beta was not decreased when either EC or lymphoid cells were preincubated with thalidomide. In conclusion, thalidomide decreases the production of several cytokines in MECLR, especially GM-CSF and TNF-alpha, which play a major role in the viability and function of Langerhans cells. This effect of thalidomide on the lymphocyte-epidermal cell interactions may, at least partly, explain the effect of thalidomide on Langerhans cell histiocytosis.