Macrophage activation by interferon: dissociation between tumoricidal capacity and suppressive activity.
Resident peritoneal macrophages (M phi) from untreated mice and inflammatory M phi induced by a sterile irritant were able to exert significant suppressive activity on lymphocyte functions. M phi-mediated suppression was evident in lymphocyte proliferation and in a proliferation-independent lymphocyte response (i.e. lymphokine production). The lymphokine macrophage-activating factor (MAF), which enhances tumoricidal capacity of inflammatory but not of resident M phi in vitro, was ineffective in modulating suppressive activity of both resident and inflammatory M phi. In contrast, a significant effect on M phi-mediated suppression was observed upon treatment with IFN-beta. In fact, suppression of lymphoproliferation and of lymphokine production by either resident or inflammatory M phi was significantly decreased or abolished by IFN-beta. Like MAF, IFN-beta was able to increase M phi cytotoxicity against tumor cells. Such as effect, however, was evident in both resident and inflammatory M phi, thus confirming different M phi activation mechanisms for MAF and IFN-beta. These data indicate that IFN-beta acts mainly on mature M phi, which thus appear as the major M phi type involved in suppression. The contrasting effects of IFN-beta on M phi suppression and on M phi-mediated cytotoxicity strongly suggest a dissociation between the 2 induction mechanisms of suppression and cytotoxicity. The in vivo relevance of these two IFN activities was demonstrated by treating mice with the potent IFN inducer polyinosinic polycytidylic acid (poly(I).poly(C). M phi from poly(I).poly(C)-primed mice simultaneously showed enhanced tumoricidal activity and complete abolishment of suppressive capacity.
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D005260:Female; D007372:Interferons / Q000494:pharmacology*; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis / Q000494:pharmacology; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000145:classification / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D011070:Poly I-C / Q000494:pharmacology
D008222:Lymphokines; D016215:Macrophage-Activating Factors; D007372:Interferons; D011070:Poly I-C