Suppressive effect of interferon-beta on development of tumoricidal activity in mouse macrophages.
The suppressive effect of IFN-alpha and IFN-beta on the induction of tumoricidal activity in mouse bone marrow-derived macrophages was investigated. Macrophages incubated for 24 hr with IFN-beta developed lower levels of cytolytic activity when stimulated with IFN-gamma and LPS, in comparison with macrophages pretreated with medium. The suppressive effect was dependent on the pretreatment dose of IFN-beta over a concentration range of 1 to 1,000 U/ml. Analysis of IFN-gamma dose response curves of IFN-beta treated macrophages showed that these cells were less sensitive to IFN-gamma. The suppressive effects were fully neutralized by an antiserum to IFN-alpha/beta. Prostaglandins were apparently not involved in this process since the addition of indomethacin to IFN-beta treated macrophages did not prevent the loss of responsiveness to activating stimuli. In contrast to the results obtained with IFN-alpha and IFN-beta, macrophages pretreated with IFN-gamma did not develop lower levels of cytolytic activity when again stimulated with IFN-gamma and LPS. These observations provide evidence for a potentially important negative regulatory role for IFN-alpha and IFN-beta in macrophage activation for tumor cell killing.
D000818:Animals; D003602:Cytotoxicity, Immunologic; D007108:Immune Tolerance / Q000187:drug effects; D007111:Immunity, Cellular; D007213:Indomethacin / Q000494:pharmacology; D007370:Interferon Type I / Q000276:immunology*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D008070:Lipopolysaccharides / Q000276:immunology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000276:immunology
D007370:Interferon Type I; D008070:Lipopolysaccharides; D007371:Interferon-gamma; D007213:Indomethacin