Cytokines in chronic inflammatory arthritis. III. Rheumatoid arthritis monocytes are not unusually sensitive to γ-interferon,but have defective γ-interferon–mediated HLA–DQ and HLA–DR induction

Macrophages present in the synovium and synovial fluid of patients with rheumatoid arthritis (RA) express large amounts of HLA–DR molecules on their surface, despite low levels of γ-interferon (γ-IFN) in the joint. To determine whether this apparent paradox is the result of increased sensitivity to γ-IFN in RA, we compared concentrations of γ-IFN that induced HLA–DR and DQ on peripheral blood monocytes of RA patients and normal donors, using fluorescence-activated cell sorter analysis. Among normal donors, highly variable sensitivity to γ-IFN was observed. Higher amounts of γ-IFN were required to induce class II major histocompatibility complex molecules on RA monocytes versus normal monocytes. The maximum amount of HLA–DR that could be induced on RA and normal monocytes was similar; however, peak levels of HLA–DQ were significantly less in RA. Monocytes from patients with other forms of chronic inflammatory arthritis had intermediate HLA–DQ expression after γ-IFN treatment. These data suggest that an increased sensitivity to γ-IFN in RA does not account for the high level of HLA–DR expression in the joint. Also, a defect in HLA–DQ and HLA–DR induction by γ-IFN was observed.