Ognibene F P, Rosenberg S A, Lotze M, Skibber J, Parker M M, Shelhamer J H, Parrillo J E
Critical Care Medicine Department, National Cancer Institute, Bethesda, Md 20892.
Chest. 1988 Oct;94(4):750-4. doi: 10.1378/chest.94.4.750.
Interleukin-2, a lymphocyte product, has well demonstrated antitumor activity in humans. Early clinical studies showed hemodynamic alterations in patients receiving the drug as antitumor immunotherapy. We serially assessed interleukin-2-associated hemodynamic parameters and left ventricular ejection fractions in five patients with neoplastic diseases unresponsive to conventional therapies. By day 4 of therapy, compared with baseline (preinterleukin-2), all patients developed tachycardia (p less than 0.01), decreased mean arterial blood pressure (p less than 0.05), increased cardiac index (p less than 0.05), and decreased systemic vascular resistance (p less than 0.01). In addition, left ventricular ejection fraction fell from 58.0 +/- 4.7 to 36.4 +/- 4.0 percent (0.05 less than p less than 0.10), which was associated with a trend toward left ventricular dilatation manifested by an increase in left ventricular end-diastolic volume index. Transient renal dysfunction was noted in all five patients, and one developed transient respiratory failure; both types of organ dysfunction recovered to baseline values after cessation of immunotherapy. Thus, interleukin-2 induces multiple reversible cardiovascular abnormalities that are similar to the hemodynamic manifestations of human septic shock.
白细胞介素-2是一种淋巴细胞产物,已在人体中充分证明具有抗肿瘤活性。早期临床研究表明,接受该药物作为抗肿瘤免疫疗法的患者会出现血液动力学改变。我们连续评估了5例对传统疗法无反应的肿瘤疾病患者的白细胞介素-2相关血液动力学参数和左心室射血分数。到治疗第4天时,与基线(白细胞介素-2治疗前)相比,所有患者均出现心动过速(p<0.01)、平均动脉血压下降(p<0.05)、心脏指数升高(p<0.05)和全身血管阻力降低(p<0.01)。此外,左心室射血分数从58.0±4.7%降至36.4±4.0%(0.05<p<0.10),这与左心室舒张末期容积指数增加所显示的左心室扩张趋势相关。所有5例患者均出现短暂性肾功能障碍,1例出现短暂性呼吸衰竭;免疫治疗停止后,这两种器官功能障碍均恢复至基线值。因此,白细胞介素-2可诱发多种可逆性心血管异常,这些异常类似于人类感染性休克的血液动力学表现。