TRICYCLIC ANTIDEPRESSANTS INDUCE APOPTOSIS IN HUMAN T-LYMPHOCYTES

Apoptosis is a form of programmed cell death that is involved in cell turnover. In the present study we show that the tricyclic antidepressa nts (TCAS) imipramine, clomipramine and citalopram induce apoptosis in human peripheral lymphocytes. Lymphocytes were incubated with these t hree drugs for up to 48 h. Apoptosis was characterized by typical nucl eosomal DNA fragmentation on agarose gel, as well as quantitated using 4'-6-diamidino-2-phenylindole (DAPI) staining and 3'-OH end-labeling of fragmented DNA at the single cell level. Apoptosis induced by TCAs was shown to be dose-dependent and could be detected after a 24 h incu bation. The optimal concentrations of the three TCAs found to induce a poptosis were 50 mu M imipramine, 20 mu M clomipramine and 180 mu M ci talopram. Furthermore, immunofluorescence and three-color flow cytomet ry were used to identify the phenotype of apoptotic cells. TCA-induced apoptosis was shown to involve exclusively T-lymphocytes. Cytotoxic T -lymphocytes were more prone to undergo apoptosis than were T-helper c ells. In conclusion the present investigation clearly demonstrates tha t TCAs exert cell biological effects upon human T-lymphocytes. Further studies are required to determine the possible clinical relevance of these findings. (C) 1998 Published by Elsevier Science Ltd on behalf o f the International Society for Immunopharmacology.