Index > Vol. 89/2009 > Iss. 3/May > pp. 245-249 > Abstract
Investigative Report | Metabolism and internal medicine, Drug development and adverse reactions, Wounds

Prostacyclin Analogue Iloprost Influences Endothelial Cell-associated Soluble Adhesion Molecules and Growth Factors in Patients with Systemic Sclerosis: A Time Course Study of Serum Concentrations

doi: 10.2340/00015555-0632

Abstract:

Systemic sclerosis is a connective tissue disorder with unclear aetiology and pathogenesis. However, there is evidence that microvascular changes belong to the early symptoms of the disease. These are associated with increased serum levels of markers of endothelium activation, such as adhesion molecules and growth factors. The stable prostacyclin analogue iloprost is licensed for vascular symptoms (Raynaud's phenomenon) and was recently shown to exert short-term effects on these markers. In this study, serum samples (n = 13) from patients with systemic sclerosis were examined for serum levels of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1, E-selectin, endothelin-1 and vascular endothelial growth factor over 6 months after iloprost infusions in order to detect possible long-term effects. Iloprost significantly reduced initially elevated levels of these markers, partly until the end of the observation period (E-selectin, VCAM-1, endothelin-1). These effects provide serological evidence for the benefits of iloprost infusions that are seen clinically in patients with systemic sclerosis.

Authors:

Philipp Rehberger, Petra Beckheinrich-Mrowka, Uwe-Frithjof Haustein and Michael Sticherling

Key words:

scleroderma; Raynaud's phenomenon; adhesion molecules; prostacyclin; iloprost.Missing

References

  1. Abraham D, Distler O. How does endothelial cell injury start? The role of endothelin in systemic sclerosis. Arthritis Res Ther 2007; 9 Suppl 2: S2.
  2. Fleming JN, Schwartz SM. The pathology of scleroderma vascular disease. Rheum Dis Clin North Am 2008; 34: 41–55. Link to article
  3. Kahaleh B. Vascular disease in scleroderma: mechanisms of vascular injury. Rheum Dis Clin North Am 2008; 34: 57–71. Link to article
  4. Denton CP, Bickerstaff MC, Shiwen X, Carulli MT, Haskard DO, Dubois RM, et al. Serial circulation adhesion molecule levels reflect disease severity in systemic sclerosis. Br J Rheumatol 1995; 34: 1048–1054. Link to article
  5. Gruschwitz MS, Hornstein OP, van den Driesch P. Correlation of soluble adhesion molecules in the peripheral blood of scleroderma patients with their in situ expression and with disease activity. J Invest Dermatol 1997; 108: 269–274. Link to article
  6. Wigley FM, Wise RA, Seibold JR, McCloskey DA, Kujala G, Medsger TA Jr, et al. Intravenous iloprost infusion in patients with Raynaud phenomenon secondary to systemic sclerosis. A multicenter, placebo-controlled, double-blind study. Ann Intern Med 1994; 120: 199–206.
  7. Mittag M, Beckheinrich P, Haustein UF. Systemic sclerosis-related Raynaud’s phenomenon: effects of iloprost infusion therapy on serum cytokine, growth factor and soluble adhesion molecule levels. Acta Dermato Venereol 2001; 81: 294–297.
  8. LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA Jr, et al. Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol 1988; 15: 202–205.
  9. Bali G, Aberer E. Iloprosttherapie bei systemischer Sklerodermie. Hautarzt 2003; 54: 845–851. Link to article
  10. Della Bella S, Molteni M, Mascagni B, Zulian C, Compasso S, Scorza R. Cytokine production in scleroderma patients: effects of therapy with either iloprost or nifedipine. Clin Exp Rheumatol 1997; 15: 135–141.
  11. Della Bella S, Molteni M, Mocellin C, Fumagalli S, Bonara P, Scorza R. Lymphocyte-endothelium interaction in systemic sclerosis and Raynaud’s phenomenon. Clin Exp Rheumatol 2001; 19: 647–654.
  12. Mayes MD. Endothelin and endothelin receptor antagonists in systemic rheumatic disease. Arthritis Rheum 2003; 48: 1190–1199. Link to article
  13. Stratton R, Shiwen X, Martini G, Holmes A, Leask A, Haberberger T, et al. Iloprost suppresses connective tissue growth factor production in fibroblasts and in the skin of scleroderma patients. J Clin Invest 2001; 108: 241–250.
  14. Sticherling M. The role of endothelin in connective tissue diseases. Rheumatology 2006; 45: iii8–iii10. Link to article
  15. Choi JJ, Min DJ, Cho ML, Min SY, Kim SJ, Lee SS, et al. Elevated vascular endothelial growth factor in systemic sclerosis. J Rheumatol 2003; 30: 1529–1533.