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


CONCLUSIONS
Our results suggest that suppression of circulating IL-6 concentrations attenuates atherogenesis in active RA.
Dessein
P H
PH
Department of Rheumatology, Johannesburg Hospital and Milpark Hospital, University of the Witwatersrand, Johannesburg, South Africa. dessein@telkomsa.net
Joffe
B I
BI
D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000503:physiopathology; D004359:Drug Therapy, Combination; D019040:E-Selectin / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D007555:Isoxazoles / Q000627:therapeutic use; D000077339:Leflunomide; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008775:Methylprednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D008911:Minocycline / Q000627:therapeutic use; D012460:Sulfasalazine / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood*
D018501:Antirheumatic Agents; D019040:E-Selectin; D007375:Interleukin-1; D015850:Interleukin-6; D007555:Isoxazoles; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D012460:Sulfasalazine; D008911:Minocycline; D000077339:Leflunomide; D008775:Methylprednisolone; D008727:Methotrexate