Suppression of growth of PHA-stimulated human lymphocytes by a novel steroid (RU 28 362) lacking the 21-OH group

RU 28 362 is a novel synthetic steroid (lacking the 21-OH group) which reacts exclusively with the glucocorticoid receptor. It is therefore chemically different from the other natural and synthetic glucocorticoids in common use which also bind to a lesser extent to receptors for other classes of steroids. Aspects of the immunosuppressive effect of RU 28 362 were studied by comparing its suppressive effects on PHA-stimulated growth of human lymphocytes with those of hydrocortisone, betamethasone and the inactive analogue, 21-deoxyhydrocortisone. RU 28 362 was more potent than either hydrocortisone or betamethasone, but all three glucocorticoids had a parallel dose-response curve in suppression of the increase in cell volume that occurs with activation during the first day in culture. In studies on the time of appearance and density of IL-2 receptors during the first 3 days in culture, RU 28 362 was also somewhat more inhibitory and had a steeper dose-response curve than hydrocortisone or betamethasone. RU 28 362 was much more inhibitory and had a steeper dose-response curve than either hydrocortisone or betamethasone in inhibiting [3H]-TdR incorporation by 3-day PHA stimulated cultures. 21-deoxyhydrocortisone did not inhibit any aspect of PHA-stimulated lymphocyte growth.