EFFECT OF THE ANTIRHEUMATIC AGENT TENIDAP ON CD3, CD4, AND CD8 EXPRESSION AND INTERLEUKIN-1 AND LEUKOTRIENE B-4 SECRETION IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS

Thymocytes that express the complete CD3-T-cell receptor (TCR) complex are CD4- and CD8-. The CD4+ T-cell population can be subdivided into at least two quite distinct subsets, TH1 and TH2 cells, based upon cytokine expression. Interleukin-1 (IL-1) appears to be required for optimal proliferation of T cells in response to antigen and it seems that in the absence of IL-1, TH2 clones proliferate less in response to antigen. Tenidap is an antirheumatic agent that has an inhibitory effect on IL-1 production. In these studies, we show that isolated human peripheral blood mononuclear cells (PBMCs) treated in vitro with Tenidap (15 mu g/mL) for 48-h incubations significantly (p < 0.05) enhanced the present of CD4+ expression compared with untreated cells (control), as determined by cyto fluorimetric analysis. Lipopolysaccharide and Bacillus Calmette-Guerin were used as positive controls. When the cells were tested for CD3 or CD8 receptor expression, no differences were found between the untreated PBMCs and the treated (15 mu Lg/mL Tenidap) cells. No change was found when cells were incubated for 72 h. Moreover, our data show a strong dose-dependent inhibitory effect of Tenidap (15 mu g/mL) on IL-1 alpha, IL-1 beta, and leukotriene B-4 secretion in PBMCs treated overnight. The increased CD4+ expression by Tenidap in PBMCs may suggest an important role for this new antirheumatic agent in immunity and may hold future therapeutic promise for diseases involving IL-1 and leukotriene B-4 as mediators.