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.
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.
Seitz
M
M
Division of Rheumatology, University Hospital, Inselspital, Bern, Switzerland.
Zwicker
M
M
Pichler
W
W
Gerber
N
N
D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D001853:Bone Marrow / Q000276:immunology / Q000502:physiology; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology*; D018950:Lipopolysaccharide Receptors; D008264:Macrophages / Q000166:cytology* / Q000276:immunology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D006684:HLA-DR Antigens; D007375:Interleukin-1; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor