Edwards M J, Schuschke D A, Abney D L, Miller F N
Department of Surgery, University of Louisville School of Medicine, Kentucky 40292.
J Surg Res. 1991 Jun;50(6):609-15. doi: 10.1016/0022-4804(91)90050-v.
Interleukin-2 has been shown to mediate the regression of metastatic cancer. However, therapeutic application has been limited by the induction of dose-dependent toxicities in normal tissues secondary to a vascular leak syndrome. To better understand the pathophysiology of this vascular leak syndrome, the earliest microvascular effects of interleukin-2 were directly observed and quantitated by intravital microscopy. The cremaster muscle of anesthetized Sprague-Dawley rats was prepared for in vivo microvascular observation. Animals were injected with fluorescein isothiocyanate-labeled albumin, and the interstitial emission intensity was used to assess macromolecular leakage. Both the intravenous injection and topical application of interleukin-2 to the cremaster muscle acutely induced the leakage of macromolecules from the microcirculation. The topical application of interleukin-2 induced macromolecular leakage without changes in central hemodynamic parameters. Furthermore, topically applied interleukin-2 did not produce changes in arteriolar or venular diameters, or in regional microvascular blood flow, which could have influenced the protein leakage. These data support the hypothesis that the acute increase in macromolecular leakage produced by interleukin-2 occurs secondary to an increase in endothelial porosity and not as a result of changes in hemodynamic or hydrostatic forces.
白细胞介素-2已被证明可介导转移性癌症的消退。然而，由于血管渗漏综合征继发的正常组织中剂量依赖性毒性的诱导，其治疗应用受到了限制。为了更好地理解这种血管渗漏综合征的病理生理学，通过活体显微镜直接观察并定量白细胞介素-2最早的微血管效应。将麻醉的Sprague-Dawley大鼠的提睾肌制备用于体内微血管观察。给动物注射异硫氰酸荧光素标记的白蛋白，并使用间质发射强度来评估大分子渗漏。将白细胞介素-2静脉注射和局部应用于提睾肌均能急性诱导微循环中大分子的渗漏。白细胞介素-2的局部应用诱导大分子渗漏，而中心血流动力学参数无变化。此外，局部应用白细胞介素-2并未引起小动脉或小静脉直径或局部微血管血流的变化，而这些变化可能影响蛋白质渗漏。这些数据支持这样的假设，即白细胞介素-2引起的大分子渗漏的急性增加是内皮孔隙率增加的继发结果，而非血流动力学或流体静力压力变化的结果。
