Effects of NPT 15392 in vitro on human leukocyte functions

NPT 15392 (Erythro-9 (2-hydroxy-3 nonyl) hypoxanthine), a novel heterocyclic immunomodulatory compound, was analyzed over a broad concentration range on a variety of human blood leukocyte functions in vitro. NPT 15392 augmented mitogen-induced lymphocyte transformation in a variable fashion; lymphocytes from 9 of 24 individuals showed significant stimulation with phytohemagglutinin at 0.01 microgram/ml of NPT 15392, and 3 of 14 and 3 of 3 showed similar augmentation with concanavalin A and pokeweed mitogen, respectively. NPT 15392 above 10 microgram/ml inhibited mitogen responses and did not itself stimulate cell division. NPT 15392 also augmented responses of lymphocytes to antigenic stimulation with Candida and Staphylococcus antigens, purified protein derivative, and allogeneic cells in a variable manner. When observed, stimulation occurred at 0.01-1 microgram/ml of NPT 15392 for Candida and Staph. and at 0.01 microgram/ml with PPD and allogeneic cells. NPT 15392 (0.01-1 microgram/ml) consistently induced suppressor cell function alone and in combination with concanavalin A. This effect is apparently mediated by T lymphocytes since suppression was not mediated by interferon, prostaglandin or histamine. In addition, NPT 15392 (0.01-10 microgram/ml) significantly augmented "active" T cell rosettes. NPT 15392 over a broad concentration range and in the presence and absence of interferon did not stimulate natural killer cell activity or antibody-dependent cellular cytotoxicity. The data indicate that NPT 15392 is a modulator of such T lymphocyte functions as proliferative response to antigen and mitogen, suppressor activity and receptor display. Such activities imply potential therapeutic use in immunodeficiency related to defects of the thymus and thymus-derived lymphocytes.