Treatment of Raynaud's phenomenon with intravenous prostaglandin E-1 alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis

Citation
M. Gardinali et al., Treatment of Raynaud's phenomenon with intravenous prostaglandin E-1 alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis, J RHEUMATOL, 28(4), 2001, pp. 786-794
Citations number
64
Categorie Soggetti
Rheumatology,"da verificare
Journal title
JOURNAL OF RHEUMATOLOGY
ISSN journal
0315162X → ACNP
Volume
28
Issue
4
Year of publication
2001
Pages
786 - 794
Database
ISI
SICI code
0315-162X(200104)28:4<786:TORPWI>2.0.ZU;2-1
Abstract
Objective. To evaluate the efficacy and safety of prostaglandin (PG) E(1)al pha -cyclodextrin for Raynaud's phenomenon (RP) secondary to systemic scler osis (SSc) and its effect on variables of immune activation and endothelial injury in SSc such as tumor necrosis factor-alpha (TNF-alpha), soluble int erleukin 2 receptor (sIL-2R), circulating intercellular adhesion molecule-1 (cICAM-1), von Willebrand factor (VWF). and tissue-type plasminogen activa tor (t-PA). Methods. We studied 36 wommen with SSc, 24 of them given three 60 mug intra venous PGE(1)alpha -cyclodextrin infusions on 5 consecutive days at 6 week intervals during the winter. RP symptoms and healing of digital lesions wer e evaluated. Twenty age matched healthy women were the controls. TNF-alpha sIL-2R, cICAM-1, VWF, and t-PA were measured after the first and last infus ion of PGE(1)alpha -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%. PGE(1)alpha -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, resp ectively. The severity of the attacks was reduced to a limited degree. In 1 2 of the 14 patients with digital lesions, these healed completely. Ten pat ients had mild side effects during treatment (headache, increased intestina l motility. flushing). TNF-<alpha>. sIL-2R, cICAM-1, vWF and t-PA plasma co ncentrations were significantly higher in patients with SSc than controls ( p < 0.05, p < 0.001). TNF-alpha, 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 PGE(1)alpha -cyclo dextrin (both p < 0.005) and further reduced after the last (p < 0.0005 and p < 0.005). Conclusion. PGE(1)<alpha>-cyclodextrin reduces RP symptoms and plasma level s of the markers of endothelial injury in SSc, suggesting that an improveme nt of endothelial dysfunction contributes to its prolonged therapeutic effe ct.