Department of Experimental and Clinical Sciences University "G. D'Annunzio" Chieti-Pescara, Italy.
G Ital Dermatol Venereol. 2013 Apr;148(2):209-16.
Aim of the study was to assess whether Iloprost treatment summer suspension modifies systemic cytokines levels, cutaneous thermal properties and functional response to a cold-induced stress in patients affected by systemic sclerosis (SSc).
Twenty-eight patients fulfilling the American College of Rheumatology (ACR) criteria for SSc were included in the study. Patients recorded number, duration and pain-severity of Raynaud phenomenon (RP). Pain-severity was determined by a visual analog scale. Cytokines expression and production in peripheral blood mononuclear cells and serum were evaluated by RT-PCR and ELISA assay. Basal finger temperature (Tb), distal-dorsal difference temperature (DTdd) and thermal recovery time (tr) from cold stress were measured by means of functional infrared imaging (fIR). Measurements were performed in late spring, during routine Iloprost therapy (1-3 days infusion of 0.5-2 ng/kg every month), and in late summer after a therapy-withdrawal period.
Deterioration of SSc patients' skin thermal properties was observed in the period of therapy withdrawal (Tb reduction and tr enhancement; no DTdd differences) despite the improvement in symptoms of RP. A reduction in IL-12/23p40 gene expression was recorded after therapy withdrawal and a direct correlation between IL-12/23p40 and IL-23p19 gene expression was observed, stronger after therapy suspension.
Our data suggest that Iloprost treatment summer suspension may induce the loss of the therapy beneficial effect on microcirculation despite the objective reduction of RP, thus favouring a continuous use of Iloprost in absence of severe side effects. Iloprost showed to modulate only IL-23 expression corroborating the idea that this cytokine is crucial for SSc development and progression.
本研究旨在评估依前列醇治疗夏季停药是否会改变系统性硬皮病患者的全身细胞因子水平、皮肤热特性和对冷应激的功能反应。
28 名符合美国风湿病学会（ACR）系统性硬皮病标准的患者纳入本研究。患者记录雷诺现象（RP）的发作次数、持续时间和疼痛严重程度。疼痛严重程度通过视觉模拟评分法（VAS）确定。通过 RT-PCR 和 ELISA 检测外周血单个核细胞和血清中细胞因子的表达和产生。通过功能红外成像（fIR）测量基础手指温度（Tb）、远端-背温差（DTdd）和冷应激后的热恢复时间（tr）。测量在春季末进行，当时正在进行依前列醇常规治疗（每月 1-3 天输注 0.5-2ng/kg），并在夏季停药后进行。
尽管 RP 症状改善，但在停药期间观察到患者皮肤热特性恶化（Tb 降低和 tr 增强；DTdd 无差异）。停药后记录到 IL-12/23p40 基因表达减少，并且观察到 IL-12/23p40 和 IL-23p19 基因表达之间存在直接相关性，停药后相关性更强。
我们的数据表明，依前列醇治疗夏季停药可能会导致尽管 RP 客观减少，但治疗对微循环有益的效果丧失，因此在没有严重副作用的情况下，建议继续使用依前列醇。依前列醇仅显示调节 IL-23 表达，这印证了这种细胞因子对系统性硬皮病发展和进展至关重要的观点。
