Iloprost therapy acutely decreases oxidative stress in patients affected by systemic sclerosis.
BACKGROUND
Oxidative stress has been considered a leading factor in the pathogenesis of systemic sclerosis (SSc). Consistently with this hypothesis the determination of urinary isoprostanes, a reliable method for evaluation of oxidative stress, has recently showed increased levels of isoprostanes in SSc patients. Data about the effect on oxidative stress of accepted therapies for SSc such as iloprost therapy are lacking.


OBJECTIVE
The aim of this prospective study was to verify whether iloprost therapy in patients with SSc acutely reduces oxidative stress assessed by determination of 8-Iso PGF<inf>2alpha</inf> urinary levels.


METHODS
urine samples were obtained before and after a five-day cycle of iloprost infusion and urinary 8-Iso PGF<inf>2alpha</inf> levels were determined using a commercially available enzyme immunoassay.


RESULTS
Consistent with previous reports, we found an increased level of oxidative stress in SSc patients with respect to healthy controls. Basal urinary 8-iso PGF<inf>2alpha</inf> levels in SSc patients were significantly higher than those in healthy controls [2002(1122-3575) pg/mg creatinine vs. 334(225.7-441) pg/mg creatinine, p<0.001]. Moreover, as expected, urinary 8-iso PGF<inf>2alpha</inf> levels after iloprost therapy were significantly lower than basal levels [1277.5 pg/mg creatinine (742.7-2017.3) vs. 2002 pg/mg creatinine (1122-3575), p=0.001] but persisted significantly elevated respect to the levels of healthy controls (p<0.001). The effect of iloprost on oxidative stress appeared significant in patients with early and limited form of disease.


CONCLUSIONS
This prospective open-label explorative study suggests that standard course of iloprost therapy may acutely reduce oxidative stress in SSc patients. This effect appears to be more consistent in the early phases and in the limited subset of disease. Further larger trials are needed to confirm our results and to explain the pathway of such reduction, its clinical significance and potential therapeutic implications.
Erre
G L
GL
Cattedra di Reumatologia, University of Sassari, Italy.
De Muro
P
P
Dellacà
P
P
Fenu
P
P
Cherchi
G M
GM
Faedda
R
R
Passiu
G
G
D000328:Adult; D000368:Aged; D015237:Dinoprost / Q000031:analogs & derivatives / Q000652:urine; D005260:Female; D006801:Humans; D016285:Iloprost / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D011446:Prospective Studies; D012595:Scleroderma, Systemic / Q000188:drug therapy* / Q000378:metabolism*; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost; D016285:Iloprost