INHIBITION OF HUMAN LAK-CELL ACTIVITY BY THE ANTI-DEPRESSANT TRIFLUOPERAZINE

The anti-depressive drug trifluoperazine (TFP) was studied on in vitro immune responses. TFP proved to be an inhibitor of lymphokine-activat ed killer (LAK) cells in its generative step, as well as in its effect or phase. Natural killer (NK) activity and interleukin-2 (IL-2) or mit ogen-induced lymphocyte proliferation were just as sensitive to the dr ug effects, whereas the division of tumor cells was more resistant. Th e mechanism through which TFP suppresses these lymphocytic systems rem ains unclear. It does not, however, affect an early stage of cellular activation as the addition of the drug as late as 24 h after the start of the culture was still inhibitory for lymphocyte mitogenesis. Neith er the expression of CD25, nor that of CD56 was affected by TFP, and e xogenous IL-2 was unable to overcome the suppression of proliferation. In relation to cell-mediated cytotoxicity, TFP partially interfered w ith the effector/target binding. However, addition of lectin to the as say did not overcome the inhibition of lysis produced by the drug. Alt hough further work remains to be done, the effect of TFP on immune res ponses must be taken into consideration when treating immunonosuppress ed patients.