Activation and differentiation of myelomonocytic cells in rheumatoid arthritis and healthy individuals--evidence for antagonistic in vitro regulation by interferon-gamma and tumor necrosis factor alpha, granulocyte monocyte colony stimulating factor and interleukin 1.

Abstract

We analyzed expression of HLA-DR and CD14 molecules on myelomonocytic cells and its regulation by various inflammatory cytokines in 6 patients with rheumatoid arthritis (RA) and 4 healthy individuals who had undergone bone marrow aspiration. At start of the bone marrow culture there was a significantly higher number of HLA-DR and CD14 positive bone marrow mononuclear cells in patients with RA than in normals. In addition, RA bone marrow mononuclear cells expressed an up to 10-fold higher mean density of both molecules than normal bone marrow mononuclear cells during the whole culture period of up to 14 days. The effect of the cytokines interferon-gamma (IFN-gamma), tumor necrosis factor alpha (TNF alpha), granulocyte monocyte colony stimulating factor (GM-CSF) and interleukin 1 (IL-1) on the expression of CD14 or HLA-DR was different: IFN-gamma strongly upregulated HLA-DR expression and down-regulated CD14 expression while TNF alpha, GM-CSF and IL-1 mainly stimulated CD14 expression on bone marrow mononuclear cells. Our data suggest that RA bone marrow mononuclear cells exhibit an activated phenotype and that TNF-alpha GM-CSF and IL-1 mainly stimulate the differentiation of bone marrow macrophages whereas IFN-gamma activates them.