Suppression of circulating interleukin-6 concentrations is associated with decreased endothelial activation in rheumatoid arthritis

Clin Exp Rheumatol. Mar-Apr 2006;24(2):161-7.

Abstract

Background: Circulating interleukin (IL)-6 concentrations are associated with endothelial activation in rheumatoid arthritis (RA).

Objective: To assess endothelial activation before and after suppression of cytokine production in RA.

Methods: Twenty-one patients (mean (SD) age 59 (9) years; disease duration 6 (4) years) were treated with intraarticular methylprednisolone acetate (417 (152) mg) together with disease modifying agent (DMARD) initiation (n = 10) or intensification (n = 11) employing methotrexate (n = 11), leflunomide (n = 8), minocyclin (n = 6) and sulphasalazine (n = 1). Disease activity, circulating cytokines (IL-1, tumor necrosis factor alpha (TNF-alpha) and IL-6) and biomarkers of endothelial activation (circulating vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1) and endothelial leukocyte adhesion molecule-1 (ELAM-1)) were evaluated before and 2 weeks after treatment.

Results: The intervention resulted in reductions in 8 disease activity markers (p < or = 0.002). Serum IL-6 concentrations decreased from 17 (2.9) to 4.9 (4.6) pg/ml (p = 0.0008). Serum IL-1 and TNF-alpha levels did not change (p > or = 0.4). Serum VCAM-1 concentrations decreased from 912 (402) to 752 (252) (p = 0.003), ICAM-1 from 398 (205) to 323 (179) (p = 0.04) and ELAM-1 from 68 (28) to 53 (25) (p = 0.02) pg/ml, respectively. Baseline rheumatoid factor titers were associated with reductions in VCAM-1 (r(s) = 0.481, p = 0.03). In multivariable regression models, decreases in circulating interleukin-6 concentrations were associated with reductions in VCAM-1 (p < 0.0001), ICAM-1 (p = 0.005) and ELAM-1 (p = 0.02) independent of changes in disease activity, weight and blood pressure.

Conclusion: Our results suggest that suppression of circulating IL-6 concentrations attenuates atherogenesis in active RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / physiopathology
  • Drug Therapy, Combination
  • E-Selectin / blood*
  • Endothelium, Vascular / metabolism*
  • Female
  • Humans
  • Injections, Intra-Articular
  • Interleukin-1 / blood
  • Interleukin-6 / blood*
  • Isoxazoles / therapeutic use
  • Leflunomide
  • Male
  • Methotrexate / therapeutic use
  • Methylprednisolone / administration & dosage
  • Methylprednisolone / therapeutic use
  • Middle Aged
  • Minocycline / therapeutic use
  • Sulfasalazine / therapeutic use
  • Tumor Necrosis Factor-alpha / analysis
  • Vascular Cell Adhesion Molecule-1 / blood*

Substances

  • Antirheumatic Agents
  • E-Selectin
  • Interleukin-1
  • Interleukin-6
  • Isoxazoles
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Sulfasalazine
  • Minocycline
  • Leflunomide
  • Methylprednisolone
  • Methotrexate