Role of IFN-gamma and alpha in IL 1 synthesis and secretion of in vitro differentiated human macrophages: a comparative study.

Human blood monocytes (Mo) cultured in vitro differentiate to macrophages (Mx) and lose the capacity to secrete interleukin 1 (IL 1) in response to endotoxin (LPS). Incubation of Mo with interferon gamma or alpha (IFN-gamma or IFN-alpha) prevented this loss of IL 1 secretory potential during the first 24 h of culture. However, there were marked differences between the two interferons if culture period was extended beyond 24 h. Incubation of Mo with IFN-gamma for 48 or 72 h induced IL 1 release in response to LPS in all the donors without exception. In contrast, 48-h incubation of Mo with IFN-alpha alpha caused IL 1 secretion (in response to LPS) in only a minority of donors, while 72-h incubation resulted in very little or no IL 1 release in all the individuals tested. Moreover, only IFN-gamma had the capacity to reinduce IL 1 secretory potential in Mx which had lost the capacity to secrete IL 1 during previous culture. These and other results suggest that IFN-alpha differs from IFN-gamma in being: a less potent IL 1 inducer, ineffective in maintaining IL 1 secretory capacity of fresh Mo for more than 48-72 h, completely unable to reinduce IL 1 secretory potential in culture-derived Mx. Thus, the two species of IFN appear to have a markedly different role in IL 1 synthesis and secretion.