Regulatory Effects on Macrophages of Human Recombinant Interferons-α

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