Decrease in circulating endothelial cell adhesion molecule and thrombomodulin levels during oral iloprost treatment in rheumatoid arthritis patients: preliminary results.
OBJECTIVE
Rheumatoid arthritis is a chronic inflammatory autoimmune disease with proinflammatory cytokines involved in its pathogenesis. Recently in vitro as well as in vivo studies have shown that iloprost, a stable prostacyclin analogue, can reduce the release of these cytokines. This study was performed to further investigate the anti-inflammatory effects of iloprost by determining plasma adhesion molecules as markers of endothelial cell activation, and plasma thrombomodulin as a parameter of endothelial cell injury in patients with rheumatoid arthritis receiving oral iloprost therapy.


METHODS
Plasma thrombomodulin levels and the values of the plasma adhesion molecules VCAM-1 (vascular cell adhesion molecule 1), E-selectin (CD62E), and ICAM-1 (intercellular adhesion molecule 1, CD 54) were measured by ELISA during a 7-day period of treatment with orally-administered iloprost in 14 patients with active rheumatoid arthritis. Finally, the same parameters were determined at the end of the observation period (1 week after the end of therapy). In addition, the disease activity was measured using the DAS (disease activity score) as well as the patients' self-assessed pain severity, and correlated with the changes of plasma adhesion molecule and thrombomodulin levels.


RESULTS
The plasma levels of all three adhesion molecules as well as of thrombomodulin significantly decreased under therapy with oral iloprost. After 1 week (day 7 of therapy), the mean percent changes from day 0 were -20.1% for VCAM-1 (p = 0.008), -21.2 for ICAM-1 (p = 0.003), -24.6% for E-selectin (p = 0.001), and -21.7% for thrombomodulin (p = 0.003). This decrease lasted up to 1 week after the end of therapy in the case of VCAM-1 (p = 0.023) and ICAM-1 (p = 0.001). Further analysis of the results revealed additional significant correlations between different parameters of clinical disease activity, thrombomodulin and adhesion molecules.


CONCLUSIONS
This study showed hints towards clinical effects in patients with rheumatoid arthritis receiving oral iloprost therapy. Pathophysiologically, the decrease of adhesion molecules points at an immunomodulating effect of iloprost. The observed thrombomodulin-lowering effect of iloprost may indicate stabilisation of endothelial cell function by diminishing endothelial cell injury.
Boehme
Michael W J
MW
Dep. of Internal Medicine IV, University of Heidelberg, Bergheimer Str. 58, D-69115 Heidelberg, Germany. m.boehme@lrabb.de
Gao
Ino K
IK
Norden
Cornelia
C
Lemmel
Ernst-Martin
EM
D000284:Administration, Oral; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D015815:Cell Adhesion Molecules / Q000097:blood*; D019040:E-Selectin / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016285:Iloprost / Q000627:therapeutic use*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy; D010147:Pain Measurement; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D018180:Thrombomodulin / Q000097:blood*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D010975:Platelet Aggregation Inhibitors; D018180:Thrombomodulin; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D016285:Iloprost