Interleukin 1 secretion by human monocytes and macrophages.

Interleukin 1 (IL-1) is generally regarded as a major regulator of T lymphocyte proliferation. Macrophages from animals and cloned tumor cell lines have been shown to produce this monokine in response to a variety of stimuli. The ability of human monocytes and macrophages to generate IL-1 is much less well characterized. We previously demonstrated that human monocytes cultured for 1-6 days transformed to macrophages but retained their capacity to support concanavalin A-driven T cell proliferation. However, cultured macrophage capacity to support antigen-driven T cell proliferation began to decline after 3 days of culture and was markedly deficient by 6 days of culture. To determine if this loss of accessory cell function was due to the inability to secrete IL-1, we measured the monokine produced by normal fresh human monocytes and macrophages cultured in vitro from monocytes. IL-1 was assayed by the mouse thymocyte proliferation method. Fresh monocytes secreted IL-1 readily in response to lipopolysaccaride and latex particles. Macrophages cultured from fresh monocytes, however, lost this ability after greater than or equal to 2 days in culture. Mixing experiments failed to demonstrate an inhibitor present in the macrophage supernatants that would suppress thymocyte proliferation. Stimulated T cells incubated with monocytes and 3-day cultured macrophages failed to prolong or promote IL-1 secretion.