EFFECTS OF KETOTIFEN ON HUMAN-LYMPHOCYTES IN-VITRO AND IN-VIVO

The effects of the antiasthmatic drug ketotifen (CAS 34580-13-7) on hu man mononuclear leukocytes were studied in vitro and in vivo. In vitro ketotifen concentration-dependently inhibited mitogen-stimulated lymp hocyte proliferation. High ketotifen concentrations also inhibited T-l ymphocyte mitogen- and adenosine triphosphate stimulated increases in intracellular Ca2+ in lymphocytes and the U937 human monocyte precurso r cell line, respectively; this involved inhibition of both Ca2+ influ x and intracellular mobilization. In in vivo experiments, treatment of healthy volunteers with 1 mg ketotifen b. i. d. for 7 d did not alter the number or subset composition of circulating lymphocytes. Moreover , the mitogen-stimulated in vitro proliferation of lymphocytes obtaine d before and after ketotifen treatment in vivo was similar. It is conc luded that high ketotifen concentrations can inhibit the activation of resting lymphocytes in vitro but standard ketotifen treatment does no t notably affect the number or function of circulating lymphocytes in vivo.