Production and modulation of interleukin 6 synthesis by synoviocytes derived from patients with arthritic disease.
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.
Rosenbaum
J T
JT
Department of Medicine, Oregon Health Sciences University, Portland 97201.
Cugnini
R
R
Tara
D C
DC
Hefeneider
S
S
Ansel
J C
JC
D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D008970:Molecular Weight; D010003:Osteoarthritis / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D013583:Synovial Membrane / Q000737:chemistry / Q000378:metabolism*
D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger