Interferons As Macrophage-activating Factors. III. Preferential Effects of Interferon-gamma on the Interleukin 1 Secretory Potential of Fresh or Aged Human Monocytes

Human peripheral blood adherent leukocytes incubated with interferon (IFN) of three different species (alpha, beta, or gamma) show an enhanced potential of IL 1 synthesis and secretion that can be revealed by a second signal provided by endotoxins or Poly IC. We have shown that recombinant IFN-gamma, compared with recombinant IFN-alpha or purified IFN-beta, has preferential effects on IL 1 secretion in fresh monocyte cultures. We have observed a progressive and profound loss of the ability of adherent cell cultures to secrete IL 1 upon aging for 4 to 12 days in vitro. IFN-gamma was found to be more efficient than IFN-alpha or -beta at maintaining (when added at the onset of the cultures) or reversing the loss (when added on the fourth day of culture) of the IL 1 secretory function. These observations suggest that the secretion of IFN-gamma during the course of immune responses may have a critical role in feeding back the cascade of interleukins in a loop of amplification, and may thereby regulate macrophage-T lymphocyte interactions.