Change of E-selectin serum levels in rheumatoid arthritis during treatment with etanercept

Background: Rheumatoid arthritis (RA) is characterised by a local and systemic chronic inflammation with the activation of the vascular endothelium. The most important initiators of vascular adhesion expressed on endothelial cells are the P and E-selectins (von Andrian), that have been detected on the inflamed synovium (McMurray) and in the peripheral blood of RA patients (Littler, McMurray). Moreover, E-selectin, expressed on endothelium, is up-regulated after exposure to TNF-alpha (McMurray). Objectives: Aim of the study was the detection of soluble E-selectin and P-selectin serum levels during anti-tumor necrosis factor (TNF) alpha therapy. Methods: We studied 18 patients with RA [M/F=2/16; mean age=49.5 (range: 22-70) yrs; mean disease duration=109 (range:18-240) months], during a 24-week-treatment of etanercept (25 mg s.c. twice weekly), evaluating the main clinical and laboratory parameters of disease activity. In each RA patient we determined soluble E-selectin and P-selectin serum levels by ELISA before and after 4 and 24-weeks. Results: Respect to baseline, the number of painful (p < 0.0003) and swollen (p < 0.0003) joints, visual analog scale of pain (p < 0.0004), HAQ (p < 0.0003), ESR (p < 0.009) and CRP (p < 0.008) were significantly reduced after etanercept 24-week-treatment. At baseline sE-Selectin levels were significantly increased in patients with RA (p < 0.00005) as compared to 15 healthy controls, matched for sex and age. We observed that sE-selectin levels were significantly reduced, respect to baseline, at 4 (p< 0.01) and 24 (p < 0.005) week-treatment with etanercept. These levels were also decreased at 24 weeks as compared with 4 weeks of anti-TNF therapy (p < 0.01). P-selectin serum levels didn't change during etanercept treatment. Conclusion: Our results suggest that TNF-alpha blockers could play a role in the inhibition of some pathways of adhesion molecule cascade in RA. In particular, etanercept seems to down-regulate serum levels of sE-selectin, that represents a specific marker of endothelial cell activation during systemic inflammation.1. von Andrian UH, Mackay CR: T-cell function and migration. N Eng J Med 5: 1020-1034, 2000.; 2. Littler AJ, Buckley CD, Wordsworth P, Collins I, Martinson J, Simmons DL: A distinct profile of six soluble adhesion molecules (ICAM-1, ICAM-3, VCAM-1, E-selectin, L-selectin and P-selectin) in rheumatoid arthritis. Br J Rheumatol 36: 164-169, 1997.; 3. McMurray RW: Adhesion molecules in autoimmune diseases. Sem Arthritis Rheum 25: 215-233, 1996