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.
D000276:Adjuvants, Immunologic; D000818:Animals; D002450:Cell Communication / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000145:classification / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000187:drug effects; D010529:Peritoneal Cavity / Q000166:cytology; D011994:Recombinant Proteins / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D007370:Interferon Type I; D011994:Recombinant Proteins; D007371:Interferon-gamma