Treatment of Raynaud's phenomenon with intravenous prostaglandin E1alpha-cyclodextrin improves endothelial cell injury in systemic sclerosis.
OBJECTIVE
To evaluate the efficacy and safety of prostaglandin (PG) E1alpha-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-alpha (TNF-alpha), 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 microg intravenous PGE1alpha-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-alpha, sIL-2R, cICAM-1, vWF, and t-PA were measured after the first and last infusion of PGEE1alpha-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%. PGE1alpha-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-alpha, 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-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 PGE1alpha-cyclodextrin (both p < 0.005) and further reduced after the last (p < 0.0005 and p < 0.005).


CONCLUSIONS
PGE1alpha-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.
Gardinali
M
M
Dipartimento di Medicina Interna, Ospedale San Gerardo, Monza, Italy.
Pozzi
M R
MR
Bernareggi
M
M
Montani
N
N
Allevi
E
E
Catena
L
L
Cugno
M
M
Bottasso
B
B
Stabilini
R
R
D000328:Adult; D000368:Aged; D000527:Alprostadil / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D015415:Biomarkers; D003505:Cyclodextrins / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology*; D005260:Female; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000503:physiopathology; D007275:Injections, Intravenous; D008875:Middle Aged; D011928:Raynaud Disease / Q000097:blood / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D012016:Reference Values; D012594:Scleroderma, Localized / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D012595:Scleroderma, Systemic / Q000150:complications*; D016896:Treatment Outcome; D047391:alpha-Cyclodextrins
D015415:Biomarkers; D003505:Cyclodextrins; D047391:alpha-Cyclodextrins; C043214:prostaglandin E1-alpha-cyclodextrin; D000527:Alprostadil