Suppression of circulating interleukin-6 concentrations is associated with decreased endothelial activation in rheumatoid arthritis
P.H. Dessein, B.I. Joffe
2006 Vol.24, N°2
PI 0161, PF 0167
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PMID: 16762151 [PubMed]
BACKGROUND:Circulating interleukin (IL)-6 concentrations are associated with endothelial activation in rheumatoid arthritis (RA).OBJECTIVES:
To assess endothelial activation before and after suppression of cytokine production in RA.
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-α) 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.
The intervention resulted in reductions in 8 disease activity markers (p ≤ 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-α levels did not change (p ≥ 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<inf>s</inf> = 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.
Our results suggest that suppression of circulating IL-6 concentrations attenuates atherogenesis in active RA.