Induction of interleukin 1 activity from macrophages by direct interaction with C8-substituted guanine ribonucleosides.

Production of an IL-1-like activity in cultures of irradiated splenic adherent cells can be elicited by the C8-substituted guanine ribonucleosides 8-bromoguanosine (8BrGuo) and 8-mercaptoguanosine (8MGuo). This report constitutes the first evidence for activation of a non-lymphocytic cell type by these agents to secrete an immunologically-active mediator. The secreted activity is mitogenic for murine thymocytes, co-stimulates these cells synergistically in the presence of concanavalin A, and co-stimulates low cell density cultures of purified B-cells in the presence of anti-mu antibodies. Production of this activity increases in a dose-dependent manner as the concentration of nucleoside is increased, both in cultures of splenic adherent cells and of the macrophage cell line P388D1. The P388D1 results indicate that this effect of the nucleoside is not mediated by another cell type, but can proceed by direct nucleoside-cell interaction. Optimal amounts of IL-1-like activity are produced after about 24 h of culture. Anti-IL-1 antibodies that neutralize the biologic activity of an IL-1 standard also eliminate the IL-1-like activity induced by 8BrGuo. These antibodies, however, fail to alter the magnitude of the primary humoral immune response to sheep erythrocytes amplified by 8BrGuo. These data indicate that C8-substituted guanosines, known intracellular stimuli for B-lymphocytes, can also induce non-lymphocytic cells (including a macrophage-like cell line) to elaborate an active principle which exhibits IL-1-like activity. These nucleosides thus are apparently able to elicit secretion of monokines, lymphokines and immunoglobulin from macrophages, T-cells and B-cells, respectively.