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

Rheumatology (Oxford). 2004 Mar;43(3):294-301. doi: 10.1093/rheumatology/keh058. Epub 2003 Dec 16.

Abstract

Objectives: 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).

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Reaction
  • Aged
  • Aged, 80 and over
  • Chi-Square Distribution
  • Cytokines / biosynthesis*
  • Cytokines / genetics
  • Female
  • Giant Cell Arteritis / drug therapy
  • Giant Cell Arteritis / immunology*
  • Glucocorticoids / therapeutic use*
  • Humans
  • Immunohistochemistry / methods
  • Interleukin-1 / biosynthesis
  • Interleukin-1 / genetics
  • Interleukin-6 / biosynthesis
  • Interleukin-6 / genetics
  • Male
  • Middle Aged
  • Prednisone / therapeutic use*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Temporal Arteries / immunology*
  • Tumor Necrosis Factor-alpha / biosynthesis
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Cytokines
  • Glucocorticoids
  • Interleukin-1
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • Prednisone