title: Correlation of interleukin-6 production and disease activity in polymyalgia rheumatica and giant cell arteritis.
abstract: OBJECTIVE
  To explore the role of proinflammatory cytokines in giant cell arteritis (GCA) and polymyalgia rheumatica (PMR), two clinically related syndromes characterized by an intense acute-phase reaction. In particular, to determine plasma concentrations of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF alpha) and to correlate changes in plasma IL-6 levels with clinical symptoms during corticosteroid therapy.
  
  
  METHODS
  IL-6 and TNF alpha concentrations were determined in plasma samples from patients with untreated PMR or GCA, and plasma IL-6 levels were monitored in patients receiving long-term therapy (14 months) with corticosteroids. To identify IL-6-producing cells, the polymerase chain reaction was used to detect IL-6 messenger RNA. In vitro production of IL-6 and IL-2 by peripheral blood mononuclear cells (PBMC) from treated and untreated patients was quantified using IL-6- and IL-2-specific bioassay systems.
  
  
  RESULTS
  IL-6 concentrations were increased in PMR and GCA patients, whereas TNF alpha concentrations were similar to those in normal donors. Administration of corticosteroids rapidly reduced the levels of circulating IL-6 but did not correct the underlying mechanism inducing the increased IL-6 production. In individual patients, changes in plasma IL-6 levels and clinical manifestations during prolonged therapy were closely correlated. Short-term withdrawal of corticosteroids, even after several months of treatment, was followed by an immediate increase in plasma IL-6 concentrations. To identify the cellular source of plasma IL-6, PBMC from treated and untreated patients with PMR or GCA were analyzed for their ability to secrete IL-6 and the T cell-specific cytokine IL-2. Polyclonal T cell stimulation caused a rapid release of IL-6, which was shown to be derived exclusively from CD14+ cells.
  
  
  CONCLUSIONS
  Increased production of IL-6, but not TNF alpha, is a characteristic finding in patients with PMR or GCA. Corticosteroids rapidly suppress IL-6 production but do not correct the underlying mechanism inducing the increased IL-6 production. The close correlation of plasma IL-6 concentrations with clinical symptoms suggests a direct contribution of this cytokine to the disease manifestations and presents the possibility that monitoring IL-6 levels would be useful in making decisions on adjustment of corticosteroid dosage in individual patients.
authors.affiliation: Department of Medicine, Mayo Clinic, Rochester, MN 55905.
authors.forename: N E
authors.initials: NE
authors.lastname: Roche
authors.forename: J W
authors.initials: JW
authors.lastname: Fulbright
authors.forename: A D
authors.initials: AD
authors.lastname: Wagner
authors.forename: G G
authors.initials: GG
authors.lastname: Hunder
authors.forename: J J
authors.initials: JJ
authors.lastname: Goronzy
authors.forename: C M
authors.initials: CM
authors.lastname: Weyand
mesh_terms: D000368:Aged; D001483:Base Sequence; D013700:Giant Cell Arteritis / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000097:blood; D008137:Longitudinal Studies; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D009994:Osmolar Concentration; D011111:Polymyalgia Rheumatica / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011241:Prednisone / Q000627:therapeutic use; D012016:Reference Values; D013601:T-Lymphocytes / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D011241:Prednisone