Anguera Ignasi, Miranda-Guardiola Faustino, Bosch Xavier, Filella Xavier, Sitges Marta, Marín José Luis, Betriu Amadeu, Sanz Ginés
Institut de Malalties Cardiovasculars, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Am Heart J. 2002 Nov;144(5):811-7. doi: 10.1067/mhj.2002.124831.
Inflammation is an important phenomenon in atherosclerotic plaque growth and in plaque instability. Cytokines are nuclear mediators in the inflammatory response; some have proinflammatory and others anti-inflammatory roles. Proinflammatory cytokines have been associated with worse outcomes in unstable angina. The aims of this study were to determine the role of the anti-inflammatory cytokine interleukin (IL)-10 and the proinflammatory to anti-inflammatory ratios in the short-term prognosis of patients with unstable angina.
Serum levels of proinflammatory cytokines IL-1beta, IL-6, and IL-8, and of the anti-inflammatory cytokine IL-10 were determined on admission in 127 consecutive patients with severe unstable angina, and comparisons were made between patients who had cardiovascular events (death, nonfatal myocardial infarction, readmission for refractory angina) (n = 20) and patients without coronary events (n = 107) during a follow-up period of 3 months.
IL-10 levels were lower (0.67 +/- 1.13 vs 1.33 +/- 1.67 pg/mL, P =.04) and IL-8 levels were higher (3.6 +/- 2.41 vs 2.23 +/- 2.47 pg/mL, P =.029) in patients in whom cardiovascular events subsequently developed compared with those without events, with resulting higher proinflammatory to anti-inflammatory cytokine ratios in the former group, whereas no significant differences were seen in IL-1beta or IL-6 levels between the groups, except for the subgroup of patients with prolonged rest angina and persistent electrocardiographic changes. A greater ratio of IL-8 to IL-10 serum levels was observed in patients who had coronary events (28 +/- 25 vs 12 +/- 21, P =.007). The risk of subsequent coronary events increased in patients in the highest quartile of proinflammatory to anti-inflammatory cytokine ratio (IL-8/IL-10). Patients in the highest quartile had a relative risk 3.8 times higher than those in the lowest quartile (P =.01).
Lower levels of IL-10, with higher proinflammatory to anti-inflammatory cytokine ratios, were observed on admission in patients with unstable angina who subsequently had cardiovascular events. Higher levels of the anti-inflammatory cytokine IL-10 may be needed to provide protection in unstable angina.
炎症是动脉粥样硬化斑块生长及斑块不稳定过程中的一个重要现象。细胞因子是炎症反应中的核介质;一些具有促炎作用,另一些具有抗炎作用。促炎细胞因子与不稳定型心绞痛的不良预后相关。本研究旨在确定抗炎细胞因子白细胞介素(IL)-10的作用以及促炎与抗炎细胞因子比值在不稳定型心绞痛患者短期预后中的作用。
对127例连续的严重不稳定型心绞痛患者入院时测定促炎细胞因子IL-1β、IL-6和IL-8以及抗炎细胞因子IL-10的血清水平,并对随访3个月期间发生心血管事件(死亡、非致命性心肌梗死、因难治性心绞痛再次入院)的患者(n = 20)和未发生冠状动脉事件的患者(n = 107)进行比较。
与未发生事件的患者相比,随后发生心血管事件的患者IL-10水平较低(0.67±1.13 vs 1.33±1.67 pg/mL,P = 0.04),IL-8水平较高(3.6±2.41 vs 2.23±2.47 pg/mL,P = 0.029),导致前一组促炎与抗炎细胞因子比值更高,而两组间IL-1β或IL-6水平无显著差异,除延长静息型心绞痛且心电图持续改变的患者亚组外。发生冠状动脉事件的患者中观察到IL-8与IL-IO血清水平比值更高(分别为28±25与12±21,P = 0.007)。促炎与抗炎细胞因子比值处于最高四分位数的患者随后发生冠状动脉事件的风险增加。处于最高四分位数的患者相对风险比最低四分位数的患者高3.8倍(P = 0.01)o
在随后发生心血管事件的不稳定型心绞痛患者入院时观察到IL-10水平较低,促炎与抗炎细胞因子比值较高。在不稳定型心绞痛中可能需要更高水平的抗炎细胞因子IL-10来提供保护。