Cardiovascular Division, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Department of Medicine, Queen's University, Kingston, Ontario, Canada.
J Heart Lung Transplant. 2018 Mar;37(3):376-384. doi: 10.1016/j.healun.2017.08.011. Epub 2017 Sep 1.
An elevated serum level of interleukin-6 (IL-6) in pulmonary arterial hypertension (PAH) patients results in a greater symptom burden and increased mortality; however, the mechanisms underlying these observations remain unclear. Because both pre-clinical and clinical data associate elevated IL-6 levels with impaired cardiac function, we hypothesized that the adverse effects of IL-6 in PAH result, in part, from right ventricular (RV) dysfunction.
We analyzed the relationship between IL-6 and RV function in 40 patients with PAH identified in our institutional PAH registry. Serum IL-6 levels was quantified by enzyme-linked immunoassay.
PAH patients had higher IL-6 levels than age- and gender-matched controls. Circulating IL-6 levels correlated inversely with echocardiography-based measures of RV function and RV-pulmonary artery (RV-PA) coupling. When dividing PAH patients by median IL-6 level, patients with higher IL-6 had significantly worse RV function (fractional area change [FAC] 23 ± 12% vs 38 ± 11%, tricuspid annular plane systolic excursion [TAPSE] 1.3 ± 0.3 cm vs 2.1 ± 0.5 cm), impaired RV-PA coupling (0.6 ± 0.5%/mm Hg vs 0.9 ± 0.5%/mm Hg), higher right atrial pressure (13 ± 7 mm Hg vs 9 ± 5 mm Hg), reduced cardiac index (2.0 ± 0.5 liters/min/m vs 2.8 ± 1.0 liters/min/m) and lower stroke volume (48 ± 20 ml vs 70 ± 28 ml). In contrast, the relationships between IL-6 and mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and pulmonary arterial compliance (PAC) were not significant. Finally, IL-6 was independently associated with RV function and RV-PA coupling after adjusting for static (PVR) and pulsatile (PAC) after-load on the RV.
Serum IL-6 levels are independently associated with RV function and RV-PA coupling in PAH. Patients with higher IL-6 levels have more severe RV dysfunction and diminished RV-PA coupling despite a comparable severity of pulmonary vascular disease.
在肺动脉高压（PAH）患者中，白细胞介素 6（IL-6）血清水平升高导致症状负担增加和死亡率增加；然而，这些观察结果的机制尚不清楚。由于临床前和临床数据均将升高的 IL-6 水平与心功能受损相关联，我们假设 IL-6 在 PAH 中的不良作用部分源自右心室（RV）功能障碍。
我们通过酶联免疫吸附试验分析了 40 例在我院 PAH 登记处确诊的 PAH 患者的 IL-6 与 RV 功能之间的关系。
PAH 患者的 IL-6 水平高于年龄和性别匹配的对照组。循环 IL-6 水平与 RV 功能和 RV-肺动脉（RV-PA）偶联的超声心动图测量值呈负相关。根据中位 IL-6 水平将 PAH 患者分为两组后，IL-6 水平较高的患者 RV 功能明显更差（分数面积变化[FAC] 23 ± 12% vs 38 ± 11%，三尖瓣环平面收缩期位移[TAPSE] 1.3 ± 0.3 cm vs 2.1 ± 0.5 cm），RV-PA 偶联受损（0.6 ± 0.5%/mmHg vs 0.9 ± 0.5%/mmHg），右心房压升高（13 ± 7 mmHg vs 9 ± 5 mmHg），心输出量降低（2.0 ± 0.5 升/分/米 vs 2.8 ± 1.0 升/分/米），每搏输出量降低（48 ± 20 ml vs 70 ± 28 ml）。相比之下，IL-6 与平均肺动脉压（mPAP）、肺血管阻力（PVR）和肺动脉顺应性（PAC）之间的关系没有统计学意义。最后，在调整 RV 的静息（PVR）和脉动（PAC）后负荷后，IL-6 与 RV 功能和 RV-PA 偶联仍呈独立相关。
血清 IL-6 水平与 PAH 患者的 RV 功能和 RV-PA 偶联独立相关。尽管肺动脉血管疾病的严重程度相当，但 IL-6 水平较高的患者 RV 功能障碍更严重，RV-PA 偶联功能降低。
