IL-6 is the principal factor produced by synovia of patients with rheumatoid arthritis that induces B-lymphocytes to secrete immunoglobulins.
First, IL-6 is produced by synovial tissue of patients with rheumatoid arthritis (RA) and is the principal mediator produced by that tissue inducing differentiation of B-lymphocytes into antibody-forming cells. The Leu-1+ subset of B-lymphocytes is induced by IL-6 to secrete rheumatoid factor (IgM with anti-Fc gamma specificity). Second, the main cell types producing IL-6 in cells dissociated from RA synovial tissue are mononuclear leukocytes. Connective tissue type cells (synoviocytes) cultured from RA synovial tissue produce IL-6 in response to IL-1 beta, and IL-6 formation is increased by TGF-beta. Glucocorticoids strongly inhibit and PGE2 slightly inhibits IL-1-induced IL-6 mRNA expression in synoviocytes. Production of IL-6 increases when undissociated RA synovial tissue is maintained in culture, thus suggesting release from inhibition by a factor or factors not yet identified. Third, the major known local effect of IL-6 in RA synovial tissue is the augmentation of antibody formation and the major known systemic effect is the induction of the synthesis by the liver of acute-phase proteins, especially C-reactive protein. Levels of circulating C-reactive protein are reported to decrease in RA patients receiving long-acting antirheumatic drugs, which would be consistent with the interpretation that immature monocyte-derived macrophages are major producers of IL-6 in these patients.
Nawata
Y
Y
Department of Immunology and Cell Biology, Syntex Research, Palo Alto, California 94304.
Eugui
E M
EM
Lee
S W
SW
Allison
A C
AC
D000917:Antibody Formation; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis*; D015850:Interleukin-6; D007378:Interleukins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics; D013583:Synovial Membrane / Q000276:immunology*
D007136:Immunoglobulins; D015850:Interleukin-6; D007378:Interleukins; D012333:RNA, Messenger