Regulatory effects on macrophages of human recombinant interferons-alpha

The regulatory effects of human recombinant and hybrid interferons-alpha (IFN-alpha) on macrophage-mediated tumoricidal activity were examined. Recombinant hybrid IFN-alpha-A/D suppressed the capacity of murine interferon-gamma (IFN-gamma) to activate mouse peritoneal macrophages to a tumorilytic state, and blocked the killing of syngeneic syngeneic melanoma target cells by macrophages previously committed to the cytotoxic phenotype with a 4-h pretreatment with IFN-gamma. This suppressive activity was limited to IFN-alpha-A/D, as IFN-alpha-A and IFN-alpha-D were not effective. In contrast, IFN-alpha-A, -D, and -A/D were all capable of activating human peripheral blood monocytes to lyse human tumor cells. When encapsulated in liposomes, only IFN-alpha-A/D maintained its monocyte activating efficacy. These findings suggest that the immunomodulatory effects of IFN-alpha subtypes and hybrid molecules are dependent on species of monocytes/macrophages, subtype, and nature of presentation to effector cells.