title: The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia inhibitory factor, and oncostatin M in rheumatoid arthritis.
abstract: OBJECTIVE
  To determine the expression of interleukin-6 (IL-6), IL-11, leukemia inhibitory factor (LIF), and oncostatin M (OSM) and their major cellular sources in the joints of rheumatoid arthritis (RA) patients, as well as the correlation of circulating levels of these IL-6-type cytokines and C-reactive protein (CRP).
  
  
  METHODS
  Messenger RNA (mRNA) and protein levels for IL-6, IL-11, LIF, and OSM were determined by using reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay, respectively.
  
  
  RESULTS
  Cells isolated from the synovium of RA patients expressed mRNA for IL-6, IL-11, LIF, and OSM at higher levels than did synovial cells from osteoarthritis (OA) patients, and spontaneously released greater quantities of these proteins in culture. Fibroblast cell lines derived from RA synovium were able to produce IL-6, IL-11, and LIF, but not OSM, when stimulated with IL-1 and tumor necrosis factor alpha. OSM was found to be produced spontaneously by synovial tissue macrophages. IL-6, IL-11, LIF, and OSM were present in synovial fluid from the RA patients; levels of IL-6, LIF, and OSM were present in significantly greater quantities in RA patients than in OA patients. However, only IL-6 was significantly elevated in the serum of RA patients and correlated with the serum CRP level, while other IL-6-type cytokines were not detected.
  
  
  CONCLUSIONS
  IL-6, IL-11, LIF, and OSM are all produced in large amounts at the site of disease activity, but IL-6 derived from synovial fibroblasts may be the major hormone-like mediator that induces the hepatic synthesis of acute-phase proteins in RA.
authors.affiliation: Okayama University Medical School, Shikato-cho, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Okamoto
authors.forename: M
authors.initials: M
authors.lastname: Yamamura
authors.forename: Y
authors.initials: Y
authors.lastname: Morita
authors.forename: S
authors.initials: S
authors.lastname: Harada
authors.forename: H
authors.initials: H
authors.lastname: Makino
authors.forename: Z
authors.initials: Z
authors.lastname: Ota
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood; D005260:Female; D006131:Growth Inhibitors / Q000097:blood; D006801:Humans; D017370:Interleukin-11 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007596:Joints / Q000737:chemistry; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000097:blood; D008297:Male; D008875:Middle Aged; D053683:Oncostatin M; D010003:Osteoarthritis / Q000097:blood; D010455:Peptides / Q000097:blood; D013583:Synovial Membrane / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; D006131:Growth Inhibitors; D017370:Interleukin-11; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; C508351:OSM protein, human; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; D053683:Oncostatin M; D002097:C-Reactive Protein