Background Iloprost is a synthetic prostaglandine used for vascular manifestation of Systemic Sclerosis (SSc), in particular it is indicated for active digital ulcers (DU) and severe Raynaud Phenomenon (RP) (1). It acts on several receptors such as IP and EP receptors and PPRs. Iloprost is also involved in the regulation of gene expression, fibrosis and inflammation (2,3,4). CXCL4 o Platelet Factor 4, is a 70KDa CXC-chemokine synthesized in megakaryocytes and plasmacytoid dendritic cells, released after platelet activation. In SSc, it seems to be higher in patients with early diffuse SSc and it correlates with mRSS and presence of PAH (5).
Objectives To evaluate the effect of Iloprost on vascular manifestations, on disease activity and on serum levels of CXCL4 at baseline (T0) and after 1 month (T1), 3 months (T3) and 6 months (T6) of therapy.
Methods 30 patients (M/F =1/29; mean age =58.2 yrs; mean disease duration =12.8 yrs) with established SSc according to ACR criteria, were enrolled. At T0, T1, T3 and T6 treatment with Iloprost at standard dosage we determined RP VAS, number of DU, European Scleroderma Study Group Activity Index (EScSGAI) and serum levels of CXCL4, measured using commercially available immunoassay kit (Human CXCL4/PF4 R&D SYSTEMS®). All patients underwent to a complete clinical, instrumental and laboratory evaluation.
Results Regarding RP VAS, we found a statistically significant increase (p=0.04) at T3, corresponding to the colder winter period, while it decreased, although not significantly at T1 and at T6, where this reduction was significant compared to T3 values (p=0.0008). Considering the number of active DU, we have highlighted the same trend of the RP VAS. EScSGAI values showed a statistically significant reduction (p=0.03) comparing T3 to T6. Regarding CXCL4, we found significantly higher levels in SSc patients respect to a group of healthy controls (HC) (p=0.047). No significant difference was found in serum levels of CXCL4 at T0, T1,T3 and T6. Evaluating patients with higher levels of CXCL4 at baseline, respect to the average of HC values (CXCL4>25,000 pg/ml) (11/30 patients), we found that 7 subjects had a significant improvement in disease activity at T6 evaluated by EScSGAI (p=0.015). In these patients we also detected a significant reduction in T3 CXCL4 values (p=0.043) persisting and at T6, although not reaching statistical significance. Moreover higher basal levels of CXCL4 in patients with disease duration less of 60 months (p=0.05) and in patients with pericardial effusion (p=0.037) were detected. Besides we found significantly lower levels of CXCL4 in patients with DU history (p=0.049) and esophageal involvement (p=0.008).
Conclusions Our study confirms the efficacy of Iloprost on vascular manifestation of SSc and also highlights its effect on the disease activity. Moreover this drug seems to influence, in a subgroup of patients, concentrations of CXCL4, an important chemokine involved in SSc pathogenesis that deserves further investigations.
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Disclosure of Interest None declared