Mechanisms of macrophage activation in rheumatoid arthritis: the role of gamma-interferon.
Gamma-interferon (gamma-IFN) is a potent inducer of surface expression of class II MHC molecules in vitro. Enhanced HLA-DR expression is a characteristic immuno-histological feature of rheumatoid joints. To assess the possible relevance of gamma-IFN to macrophage (M phi) activation in rheumatoid arthritis (RA) we investigated the spontaneous and mitogen-induced production of gamma-IFN by RA lymphocytes using a sensitive radioimmunoassay. Synovial fluids (SF) from a variety of inflammatory and non-inflammatory rheumatic diseases did not contain measurable amounts of IFN. RA lymphocytes from peripheral blood (PBL) and joints failed to show spontaneous gamma-IFN production. RA and control PBL were equally responsive to both mitogen stimulation and to the addition of exogenous interleukin 2 (IL-2) as control PBL. SF lymphocytes from RA patients showed a significantly decreased PHA-stimulated gamma-IFN production and this was in contrast to the SF lymphocytes from patients with other inflammatory joint diseases who showed significantly increased gamma-IFN production compared with matched PB lymphocytes. These results show that gamma-IFN production by peripheral blood and joint cells from patients with RA is normal and it remains to be established whether gamma-IFN is the factor responsible for the macrophage activation seen in the disease.
D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000494:pharmacology; D008214:Lymphocytes / Q000276:immunology; D008262:Macrophage Activation; D008297:Male; D008875:Middle Aged; D010835:Phytohemagglutinins / Q000494:pharmacology; D013582:Synovial Fluid / Q000276:immunology; D013583:Synovial Membrane / Q000276:immunology
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D010835:Phytohemagglutinins; D007371:Interferon-gamma