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首页> 外文期刊>Journal of immunotherapy >Effects of isolated limb perfusion with tumor necrosis factor-alpha on circulating levels of proinflammatory cytokines.
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Effects of isolated limb perfusion with tumor necrosis factor-alpha on circulating levels of proinflammatory cytokines.

机译：肢体肿瘤坏死因子-α灌注对循环中促炎细胞因子水平的影响。

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摘要

Hyperthermic isolated limb perfusion (ILP) with tumor necrosis factor-a (TNFalpha) and cytotoxic drugs is currently used for treatment of melanoma and sarcoma of the limbs. Tumor necrosis factor-alpha is involved in the systemic inflammatory response syndrome as a result of activation of inflammatory cells and production of bioactive substances. The goal of this study was to determine the circulating levels of proinflammatory cytokines and soluble adhesion molecules in 19 patients with limb melanoma or sarcoma undergoing ILP with (n = 9) or without TNFalpha (n = 10). The results obtained demonstrated that ILP with TNFalpha was responsible for a leakage of TNFalpha in the systemic circulation, followed by a rise in interleukin (IL)-6 and IL-8 levels within I h. Elevated soluble (s)P-selectin levels were found 1-3 h after ILP. Plasma sE-selectin peaked 6-9 h after ILP, and soluble vascular cell adhesion molecule (sVCAM) levels reached a maximum after 24 h. Significant correlations were observed among these variables, confirming the interdependence of all changes observed. On the other hand, ILP with cytotoxic drugs alone induced only a modest release of TNFalpha, which was not followed by an immediate rise in IL-6 and IL-8. Four of the 9 patients undergoing ILP with TNF had severe systemic toxicity. No association was found between systemic TNF levels and the clinical outcome, whereas elevated TNF perfusion levels as well as systemic IL-6 and IL-8 levels were constantly elevated in patients with severe toxicity. These results are suggestive of an important role of TNFalpha levels in the perfusion system (more than leakage of perfusate) in causing postoperative toxicity, although other ILP-related factors should not be excluded.
机译：目前，使用带有肿瘤坏死因子-a（TNFalpha）和细胞毒性药物的高温隔离肢体灌注（ILP）治疗肢体黑色素瘤和肉瘤。由于炎性细胞的活化和生物活性物质的产生，肿瘤坏死因子-α参与了全身性炎性反应综合征。这项研究的目的是确定19例肢体黑色素瘤或肉瘤接受ILP（n = 9）或不接受TNFα（n = 10）的患者中促炎细胞因子和可溶性粘附分子的循环水平。所获得的结果表明，具有TNFα的ILP导致体液循环中TNFα的泄漏，随后在1小时内白介素（IL）-6和IL-8水平升高。 ILP后1-3小时发现可溶性（s）P-选择素水平升高。血浆sE-选择素在ILP后6-9小时达到峰值，而可溶性血管细胞粘附分子（sVCAM）的水平在24小时后达到最大值。在这些变量之间观察到显着的相关性，证实了所观察到的所有变化的相互依赖性。另一方面，单独使用细胞毒性药物的ILP只能诱导TNFα的适度释放，而IL-6和IL-8不会立即升高。接受ILP TNF治疗的9例患者中有4例具有严重的全身毒性。在全身性TNF水平与临床结果之间未发现关联，而严重毒性患者的TNF灌注水平以及全身性IL-6和IL-8水平持续升高。这些结果表明，TNFα水平在灌注系统中的作用（大于灌注液的泄漏）在引起术后毒性中起着重要作用，尽管不应排除其他与ILP相关的因素。

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