EFFECTS OF CYCLOPHOSPHAMIDE ON IN VITRO HUMAN LYMPHOCYTE CULTURE AND MITOGENIC STIMULATION

Publisher Website
Google Scholar
Abstract
Cyclophosphamide (CY) may be inactive in vitro under certain conditions. CY was tested for its ability to inhibit human lymphocyte proliferation and to modulate lymphocyte response to mitogens in vitro. The inhibition of or the increase in 3H-thymidine incorporation in mitogen-stimulated and unstimualted lymphocytes by CY was used as a measure of CY activity in vitro. Lymphocytes from 10 different persons had a mean decrease of 74% in 3H-thymidine incorporation in the presence of CY (P < 0.005). The effect was maximal at a concentration of 160 .mu.g/ml. A mean inhibition of 35 and 55% was caused by 10 and 40 .mu.g/ml concentrations of CY, respectively. CY also reduced the number of viable cells during 5 days in culture and had a profound effect on mitogen stimulation of lymphocytes. CY modulated the stimulation of lymphocytes. CY modulated the stimulation of lymphocytes by phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) either by augmenting or suppressing the responses. At low concentrations (10 .mu.g/ml) it augmented mitogenic stimulation by 46-281%. At higher concentrations (20-160 .mu.g/ml), CY had a suppressive effect with a maximum suppression of 99%. The CY-induced immunomodulation may be caused by its action on the regulatory T cells. When tested in vitro, CY had inhibitory activity on T cells.