Kinetic analysis of the immunopotentiating effect of the hypoxanthine analogue, NPT-15392, on the interleukin-2 production potential of human lymphocytes.

Previous studies have shown that NPT-15392 (9-erythro-(2-hydroxy, 3-nonyl) hypoxanthine) enhances a variety of lymphoid functional activities including proliferative responses to various antigenic and mitogenic stimuli. In order to account at least partially for this immunopotentiation by NPT-15392, we examined the effects of this compound on interleukin-2 (IL-2) production by cultures of mitogen-activated human peripheral blood mononuclear cells (PBMC). Coculture of PBMC with NPT-15392 and concanavalin A (Con A) for 24 h resulted in significant increase of IL-2 in the supernatants of such cultures as compared with the IL-2 levels of control, non-NPT-treated, Con A-activated cultures. This enhancing effect was demonstrable with final culture concentrations of NPT-15392 ranging from 0.1 to 0.5 microgram/ml. Doses of NPT-15392 in excess of 5.0 micrograms/ml resulted in modest suppression of net IL-2 production. Pretreatment of PBMC with NPT-15392 for 2-4 h prior to activation with Con A was sufficient to achieve maximum enhancement of IL-2 production (20-40% average increase). Exposure of PBMC to NPT-15392 for longer periods (i.e. 24 h) did not result in higher levels of IL-2 production. NPT-15392 alone did not induce IL-2 synthesis at any of the doses employed and did not induce proliferation of the IL-2-dependent target cells used to quantitate IL-2 activity. Because of the multipotential role of IL-2 in the immune system, enhancement of IL-2 production by NPT-15392 may be a central pathway whereby this compound augments many lymphoid effector functions.