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Production and modulation of interleukin 6 synthesis by synoviocytes derived from patients with arthritic disease.
  1. J T Rosenbaum,
  2. R Cugnini,
  3. D C Tara,
  4. S Hefeneider,
  5. J C Ansel
  1. Department of Medicine, Oregon Health Sciences University, Portland 97201.

    Abstract

    Interleukin 6 (IL-6) is a potent cytokine, the biological activities of which include the stimulation of immunoglobulin secretion, T cell activation, induction of the acute phase response, activation of megakaryocytes, and pyrogenicity. These biological activities make it a plausible contributor to rheumatoid arthritis. The ability of synoviocytes to synthesise this potential mediator of inflammation was tested. Cultures of fibroblast-like cells were established from joint tissue from patients with rheumatoid arthritis, degenerative joint disease, or trauma. Supernatants from synoviocytes from each diagnostic category contained IL-6-like activity as detected in a B9 plasmacytoma cell proliferation assay. Supernatants from IL-1 stimulated synoviocytes from patients with rheumatoid arthritis (n = 5) contained an average of 70,000 U/ml IL-6. Western blot analysis confirmed that these supernatants contained peptides that reacted with a highly specific antibody to IL-6. A cDNA probe specific for IL-6 hybridised with mRNA derived from synoviocytes representative of each disease state. Interleukin 6 mRNA expression increased by culturing synoviocytes in the presence of 10% calf serum, IL-1 (30 U/ml), insulin (166 ng/ml), or basic fibroblast growth factor (16 ng/ml). In contrast, dexamethasone (10(-6) mol/l) suppressed the ability of IL-1 to increase the expression of IL-6 mRNA. Recombinant IL-6 itself did not detectably upregulate its own message. The regulation of production of IL-6 by synoviocytes may be important in the pathogenesis of joint inflammation.

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