Treatment of Raynaud's phenomenon with intravenous prostaglandin E1α-cyclodextrin improves endothelial cell injury in systemic sclerosis

M. Gardinali, M. R. Pozzi, M. Bernareggi, N. Montani, E. Allevi, L. Catena, M. Cugno, B. Bottasso, R. Stabilini

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. To evaluate the efficacy and safety of prostaglandin (PG) E1α-cyclodextrin for Raynaud's phenomenon (RP) secondary to systemic sclerosis (SSc) and its effect on variables of immune activation and endothelial injury in SSc such as tumor necrosis factor-α (TNF-α), soluble interleukin 2 receptor (sIL-2R), circulating intercellular adhesion molecule-1 (cICAM-1), von Willebrand factor (vWF), and tissue-type plasminogen activator (t-PA). Methods. We studied 36 women with SSc, 24 of them given three 60 μg intravenous PGE1α-cyclodextrin infusions on 5 consecutive days at 6 week intervals during the winter. RP symptoms and healing of digital lesions were evaluated. Twenty age matched healthy women were the controls. TNF-α, sIL-2R, cICAM-1, vWF, and t-PA were measured after the first and last infusion of PGE1α-cyclodextrin and correlated with clinical features. Results. RP symptoms' improved in 87% of the patients. The benefit of each 5 day cycle lasted 4 or more weeks in 75%. PGE1α-cyclodextrin reduced the daily frequency of RP symptoms by 20% (p <0.05), 41% (p <0.005), and 53% (p <0.0005) from baseline after the 1st, 2nd, and 3rd infusions, respectively. The severity of the attacks was reduced to a limited degree. In 12 of the 14 patients with digital lesions, these healed completely. Ten patients had mild side effects during treatment (headache, increased intestinal motility, flushing). TNF-α, sIL-2R, cICAM-1, vWF, and t-PA plasma concentrations were significantly higher in patients with SSc than controls (p <0.05, p <0.001). TNF-α, sIL-2R, and cICAM-1 were higher in diffuse SSc and patients with lung involvement. The plasma levels of cICAM-1 and t-PA were significantly reduced after the 1st infusion of PGE1α-cyclodextrin (both p <0.005) and further reduced after the last (p <0.0005 and p <0.005). Conclusion. PGE1α-cyclodextrin reduces RP symptoms and plasma levels of the markers of endothelial injury in SSc, suggesting that an improvement of endothelial dysfunction contributes to its prolonged therapeutic effect.

Original languageEnglish
Pages (from-to)786-794
Number of pages9
JournalJournal of Rheumatology
Volume28
Issue number4
Publication statusPublished - 2001

Keywords

  • Intercellular adhesion molecule-1
  • Prostaglandins
  • Raynaud's phenomenon
  • Systemic sclerosis
  • Tissue-type plasminogen activator

ASJC Scopus subject areas

  • Rheumatology
  • Immunology

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