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

Arthritis Rheum. 1989 Sep;32(9):1074-9. doi: 10.1002/anr.1780320904.

Abstract

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 gamma-interferon (gamma-IFN) in the joint. To determine whether this apparent paradox is the result of increased sensitivity to gamma-IFN in RA, we compared concentrations of gamma-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 gamma-IFN was observed. Higher amounts of gamma-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 gamma-IFN treatment. These data suggest that an increased sensitivity to gamma-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 gamma-IFN was observed.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • Biological Factors / immunology*
  • Cell Separation
  • Cells, Cultured
  • Cytokines
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Female
  • Flow Cytometry
  • HLA-DQ Antigens / analysis*
  • HLA-DR Antigens / analysis*
  • Humans
  • Interferon-gamma / pharmacology*
  • Male
  • Middle Aged
  • Monocytes / drug effects*
  • Monocytes / immunology

Substances

  • Biological Factors
  • Cytokines
  • HLA-DQ Antigens
  • HLA-DR Antigens
  • Dexamethasone
  • Interferon-gamma