Mazzone A, Faggioli P, Cusa C, Stefanin C, Rondena M, Morelli B
U.O. Internal Medicine and Onclogy, Ospedale Civile di Legnano, Legnano, Milan, Italy.
Eur J Clin Invest. 2002 Dec;32(12):882-8. doi: 10.1046/j.1365-2362.2002.01095.x.
Iloprost has beneficial effects on microcirculation by preventing platelet and leukocyte reciprocal activation, which is known to lead to endothelial damage and acute thrombosis. This drug also reduces inflammatory system activation by decreasing alpha M beta 2 integrin expression on the phagocyte membrane, might have a role in the protection and restoration of endothelial integrity and might interact with coagulation cascade activation.
Forty patients were enrolled: 29 with systemic sclerosis (SSc) and 11 with peripheral artery disease (PAD). Iloprost was administered for 5 days in the first group and for 21 days in second group of patients. To ascertain whether iloprost modifies the parameters of endothelial and coagulation cascade activations, the plasma concentrations of S-ICAM-1 and F1 + 2 were detected in patients at baseline, after 5 days and, in PAD patients only, after 21 days of iloprost therapy. S-ICAM-1 is the endothelial counter receptor for alpha M beta 2 integrin and is a marker of endothelial cell activation; and F1 + 2 is a marker of coagulation cascade activation.
After infusion of iloprost a significant decrease of S-ICAM-1 was observed in both the SSc (P < 0.002) and PAD patients (P < 0.004). Similarly, a significant decrease of F1 + 2 was observed in the SSc (P < 0.0004) and PAD patients (P < 0.003).
The study provides evidence that iloprost reduces endothelial cells and coagulation cascade activations. Both of these mechanisms are responsible for improvement in microvascular functional capacity and for the long-term clinical benefit observed. After iloprost infusion, the SSc patients showed marked reductions in F1 + 2 and S-ICAM-1 concentrations that were statistically more significant relative to the PAD patients.
伊洛前列素可通过防止血小板和白细胞相互激活而对微循环产生有益作用,已知血小板和白细胞相互激活会导致内皮损伤和急性血栓形成。该药物还可通过降低吞噬细胞膜上αMβ2整合素的表达来减少炎症系统激活,可能在内皮完整性的保护和恢复中发挥作用,并且可能与凝血级联激活相互作用。
纳入40例患者:29例系统性硬化症(SSc)患者和11例外周动脉疾病(PAD)患者。第一组患者接受伊洛前列素治疗5天,第二组患者接受治疗21天。为确定伊洛前列素是否改变内皮和凝血级联激活参数,在基线时、5天后检测患者血浆中S-ICAM-1和F1 + 2的浓度,仅在PAD患者中于伊洛前列素治疗21天后检测上述指标。S-ICAM-1是αMβ2整合素的内皮细胞对应受体,是内皮细胞激活的标志物;F1 + 2是凝血级联激活的标志物。
输注伊洛前列素后,SSc患者(P < 0.002)和PAD患者(P < 0.004)的S-ICAM-1均显著降低。同样,SSc患者(P < 0.0004)和PAD患者(P < 0.003)的F1 + 2也显著降低。
该研究提供证据表明伊洛前列素可降低内皮细胞和凝血级联激活。这两种机制均有助于改善微血管功能能力以及实现所观察到的长期临床获益。输注伊洛前列素后,SSc患者的F1 + 2和S-ICAM-1浓度显著降低,相对于PAD患者,其统计学意义更为显著。