Gérain J, Liénard D, Pampallona S, Baumgartner M, Rüegg C, Buurman W A, Eggermont A, Lejeune F
Centre pluridisciplinaire d'Oncologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Cytokine. 1997 Dec;9(12):1034-42. doi: 10.1006/cyto.1997.0247.
Isolated limb perfusion (ILP) with high dose tumour necrosis factor (TNF), interferon gamma and melphalan (TIM) is an efficient treatment for patients with regionally advanced melanoma and sarcoma. In 44 patients, we determined the kinetics of soluble TNF receptors (sTNF-RI and RII) plasma concentrations, and correlated them with systemic TNF and interleukin 6 (IL-6) levels and shock. Seven patients treated conventionally by ILP without cytokine served as controls. Elevated levels of both sTNF-Rs were observed within 30 min after beginning of the TIM-ILP. A first peak of sTNF-Rs levels was observed 3 h after ILP and was followed by a rapid decrease reaching a nadir at 12-14 h post ILP. This first peak was followed by a second, long-lasting elevation of both sTNF-Rs levels persisting for 4 to 5 days after TIM-ILP. Patients treated by ILP without TNF/interferon gamma (IFN-gamma) had no detectable increase in either sTNF-Rs or in circulating TNF, demonstrating that the release of TNF-Rs was dependent upon the administration of TNF/IFN-gamma. High plasma levels of TNF and IL-6 were observed in patients that had more than 5% leakage during the TIM-ILP, but no significant correlation between TNF levels and the peak values of both sTNF-Rs was observed. The levels of TNF and IL-6 were, however, significantly related to each other. TNF systemic levels, but not sTNF-Rs concentrations, correlated significantly with the severity of the shock observed after TIM-ILP. Patients in which sTNF-RII concentration was in excess over circulating TNF, had no shock or grade I shock only, suggesting that sTNF-RII may play a protective, although limited, role in inhibiting activity of circulating TNF.
采用高剂量肿瘤坏死因子（TNF）、干扰素γ和马法兰（TIM）进行的隔离肢体灌注（ILP）是治疗局部晚期黑色素瘤和肉瘤患者的一种有效方法。在44例患者中，我们测定了可溶性TNF受体（sTNF-RI和RII）血浆浓度的动力学，并将其与全身TNF和白细胞介素6（IL-6）水平及休克情况进行关联。7例接受不含细胞因子的传统ILP治疗的患者作为对照。在TIM-ILP开始后30分钟内观察到两种sTNF-Rs水平均升高。ILP后3小时观察到sTNF-Rs水平的第一个峰值，随后迅速下降，在ILP后12 - 14小时达到最低点。在这个第一个峰值之后，两种sTNF-Rs水平出现第二次长期升高，在TIM-ILP后持续4至5天。接受不含TNF/干扰素γ（IFN-γ）的ILP治疗的患者，其sTNF-Rs或循环TNF均未检测到增加，表明TNF-Rs的释放依赖于TNF/IFN-γ的给药。在TIM-ILP期间渗漏超过5%的患者中观察到高血浆水平的TNF和IL-6，但未观察到TNF水平与两种sTNF-Rs的峰值之间存在显著相关性。然而，TNF和IL-6的水平彼此显著相关。TNF全身水平而非sTNF-Rs浓度与TIM-ILP后观察到的休克严重程度显著相关。sTNF-RII浓度超过循环TNF的患者，仅出现无休克或I级休克，这表明sTNF-RII可能在抑制循环TNF活性方面发挥保护作用，尽管作用有限。
