Lei D, Jerome E H, Douguet D, Jesmok G J, Schuster D P, Johnson C W, Staub N C
Department of Anesthesia, University of California, San Francisco 94143.
J Appl Physiol (1985). 1994 Feb;76(2):909-15. doi: 10.1152/jappl.1994.76.2.909.
Interleukin-2 (IL-2) is reputed to cause pulmonary microvascular injury. We studied the pulmonary and splanchnic microcirculation of anesthetized sheep after one dose (1.8 x 10(6) IU/kg) of IL-2 (n = 9) and after six doses (1.8 x 10(6) IU.kg-1.dose-1) of IL-2 over 3 days (n = 9). Seven control sheep received only 5% dextrose diluent. We measured hemodynamics and lymph dynamics in anesthetized sheep after the final dose of IL-2 or diluent. After one dose of IL-2, caudal mediastinal node (mainly pulmonary) lymph flow was stable, whereas thoracic duct lymph flow increased from a baseline of 54 +/- 6 to 124 +/- 22 ml/h. After 3 days of IL-2, the caudal mediastinal node lymph flow increased from 7.7 +/- 5.5 to 19.0 +/- 14.8 ml/h 5-6 h after the final dose of IL-2, and thoracic duct lymph flow increased from 84 +/- 43 to 143 +/- 42 ml/h. The lymph-to-plasma protein concentration ratio increased after IL-2 for thoracic duct but not for caudal mediastinal node lymph. The equilibration rate of 125I-albumin from plasma to caudal mediastinal node lymph did not change, whereas plasma-to-thoracic duct lymph equilibration was faster after both one dose and 3 days of IL-2. Positron emission tomography showed no increase in the pulmonary transcapillary escape rate for 68Ga-labeled transferrin or in extravascular lung water (n = 4). We conclude that IL-2 at doses two to three times those used clinically does not significantly injure the pulmonary microcirculation of sheep.
白细胞介素-2（IL-2）被认为可导致肺微血管损伤。我们研究了麻醉绵羊在单次注射（1.8×10⁶IU/kg）IL-2（n = 9）后以及在3天内注射六次（1.8×10⁶IU·kg⁻¹·剂量⁻¹）IL-2（n = 9）后的肺和内脏微循环。七只对照绵羊仅接受5%葡萄糖稀释液。在最后一剂IL-2或稀释液后，我们测量了麻醉绵羊的血流动力学和淋巴动力学。单次注射IL-2后，尾侧纵隔淋巴结（主要是肺部）淋巴流量稳定，而胸导管淋巴流量从基线的54±6增加到124±22 ml/h。注射IL-2 3天后，在最后一剂IL-2后5 - 6小时，尾侧纵隔淋巴结淋巴流量从7.7±5.5增加到19.0±14.8 ml/h，胸导管淋巴流量从84±43增加到143±42 ml/h。IL-2注射后，胸导管淋巴的淋巴与血浆蛋白浓度比值增加，但尾侧纵隔淋巴结淋巴未增加。从血浆到尾侧纵隔淋巴结淋巴的¹²⁵I - 白蛋白平衡率没有变化，而在单次注射和注射IL-2 3天后，血浆到胸导管淋巴的平衡都更快。正电子发射断层扫描显示，对于⁶⁸Ga标记的转铁蛋白，肺毛细血管跨膜逸出率或血管外肺水没有增加（n = 4）。我们得出结论，临床使用剂量两到三倍的IL-2不会显著损伤绵羊的肺微循环。
