Della Bella S, Molteni M, Mascagni B, Zulian C, Compasso S, Scorza R
Institute of Internal Medicine, Infectious Diseases and Immunopathology, IRCCS Ospedale Maggiore di Milano, Italy.
Clin Exp Rheumatol. 1997 Mar-Apr;15(2):135-41.
To compare the long-term effects of intermittent infusion of iloprost with those of oral nifedipine on the in vitro production of cytokines in patients with systemic sclerosis (SSc), and to evaluate their relationship with the effects of the two treatments on clinical parameters.
The production of cytokines by alloactivated circulating mononucleated cells was assessed before and after one year of treatment in a subset of 31 patients enrolled in a 12-month randomized clinical trial. Nineteen patients were treated with a 5-day (8 hr per day), 2.0 ng/kg per minute infusion followed by a 1-day infusion every 6 weeks; 12 patients were treated with an oral slow-release formulation of nifedipine, 20 mg twice daily. Quantitative determinations of interleukin-1 beta (IL1-beta) and interleukin-6 (IL6) in the culture supernatants were performed with a commercial ELISA; the levels of tumor necrosis factor-alpha (TNF-alpha), and interferon-gamma (IFN-gamma) were measured by specific radioimmunometric assays.
The production of IL1-beta was significantly lower in the iloprost group than in the nifedipine group. Both the cutaneous fibrosis and the capillaroscopic patterns were better in patients treated with iloprost than in patients treated with nifedipine. There was a significant positive covariance between IL1-beta changes and the changes in both the skin score and the capillaroscopic score.
There are several mechanisms by which iloprost could exert its clinical efficacy. Vasodilatation and inhibition of platelet aggregation are certainly important, but they are transient. We suggest that the long-lasting modulation of the cytokine network observed in the present study could be another potential mechanism responsible for the persistent efficacy of iloprost despite its intermittent administration.
比较伊洛前列素间歇输注与口服硝苯地平对系统性硬化症（SSc）患者细胞因子体外产生的长期影响，并评估它们与两种治疗对临床参数影响的关系。
在一项为期12个月的随机临床试验中，对31例患者的一个亚组在治疗1年前和1年后评估同种异体激活的循环单核细胞产生细胞因子的情况。19例患者接受为期5天（每天8小时）、每分钟2.0 ng/kg的输注，随后每6周进行1天的输注；12例患者接受口服缓释硝苯地平制剂治疗，每日2次，每次20 mg。用商业酶联免疫吸附测定法（ELISA）对培养上清液中的白细胞介素-1β（IL1-β）和白细胞介素-6（IL6）进行定量测定；用特异性放射免疫测定法测量肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的水平。
伊洛前列素组IL1-β的产生明显低于硝苯地平组。接受伊洛前列素治疗的患者皮肤纤维化和毛细血管镜检查模式均优于接受硝苯地平治疗的患者。IL1-β变化与皮肤评分和毛细血管镜评分变化之间存在显著的正协方差。
伊洛前列素发挥临床疗效有多种机制。血管舒张和抑制血小板聚集肯定很重要，但它们是短暂的。我们认为，本研究中观察到的细胞因子网络的持久调节可能是另一个潜在机制，尽管伊洛前列素是间歇性给药，但它仍具有持续疗效。
