title: Tissue production of pro-inflammatory cytokines (IL-1beta, TNFalpha and IL-6) correlates with the intensity of the systemic inflammatory response and with corticosteroid requirements in giant-cell arteritis.
abstract: OBJECTIVE
  To investigate proinflammatory cytokine expression in temporal arteries from patients with giant-cell arteritis (GCA) and to analyse its relationship with the intensity of the initial systemic inflammatory reaction and response to corticosteroid therapy.
  
  
  METHODS
  Quantification of interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and interleukin-6 (IL-6) mRNA by real-time quantitative PCR in temporal artery samples from 36 patients with biopsy-proven GCA and 11 controls. Immunohistochemical detection of IL-1beta, TNFalpha, and IL-6 in temporal artery sections from 74 patients with GCA and 15 controls. Clinical and biochemical parameters of inflammation as well as the time (weeks) required to reach a maintenance prednisone dose <10 mg/day were recorded.
  
  
  RESULTS
  IL-1beta (13.8 +/- 2.5 vs 5.4 +/- 1.3 relative units, P = 0.012) and IL-6 transcripts (34 +/- 13.7 vs 7.8 +/- 4.5 relative units, P = 0.034) were significantly more abundant in patients with a strong systemic inflammatory response compared with those with no inflammatory parameters. Immunohistochemical scores for IL-1beta (2.7 +/- 0.3 vs 1.9 +/- 0.2, P = 0.018), TNFalpha (3.2 +/- 0.2 vs 2.4 +/- 0.3, P = 0.028) and IL-6 (3 +/- 0.2 vs 2.1 +/- 0.3, P = 0.023) were also significantly higher in patients with strong systemic inflammatory reaction. A significant correlation was found between the amount of tissue TNFalpha mRNA and the time required to reach a maintenance dose of prednisone <10 mg/day (r = 0.586, P = 0.001).
  
  
  CONCLUSIONS
  GCA patients with a strong systemic inflammatory response, who have been previously shown to be more resistant to corticosteroid therapy, have elevated tissue expression of proinflammatory cytokines IL-1beta, TNFalpha and IL-6. High production of TNFalpha is associated with longer corticosteroid requirements.
authors.affiliation: Vasculitis Research Unit, Department of Internal Medicine, Hospital Clinic, University of Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Villaroel 170, 08036 Barcelona, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Hernández-Rodríguez
authors.forename: M
authors.initials: M
authors.lastname: Segarra
authors.forename: C
authors.initials: C
authors.lastname: Vilardell
authors.forename: M
authors.initials: M
authors.lastname: Sánchez
authors.forename: A
authors.initials: A
authors.lastname: García-Martínez
authors.forename: M J
authors.initials: MJ
authors.lastname: Esteban
authors.forename: C
authors.initials: C
authors.lastname: Queralt
authors.forename: J M
authors.initials: JM
authors.lastname: Grau
authors.forename: A
authors.initials: A
authors.lastname: Urbano-Márquez
authors.forename: A
authors.initials: A
authors.lastname: Palacín
authors.forename: D
authors.initials: D
authors.lastname: Colomer
authors.forename: M C
authors.initials: MC
authors.lastname: Cid
mesh_terms: D000210:Acute-Phase Reaction; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D013700:Giant Cell Arteritis / Q000188:drug therapy / Q000276:immunology*; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013699:Temporal Arteries / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
chemical_list: D016207:Cytokines; D005938:Glucocorticoids; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D011241:Prednisone