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首页> 外文期刊>Cytokine >Effects of hyperthermia and tumour necrosis factor on inflammatory cytokine secretion and procoagulant activity in endothelial cells.
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Effects of hyperthermia and tumour necrosis factor on inflammatory cytokine secretion and procoagulant activity in endothelial cells.

机译：热疗和肿瘤坏死因子对内皮细胞炎性细胞因子分泌和促凝血活性的影响。

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The application of hyperthermia (HT) and tumour necrosis factor alpha (TNF) in isolation perfusion of the limb or liver results in regression of advanced cancers confined to these regions of the body in most patients and are thought to exert anti-tumour effects primarily on tumour neovasculature. However, the individual contribution of either treatment factor on endothelial cells (EC) are not known. In this study, we investigated the in vitro effects of moderate and severe HT on human umbilical vein EC (HUVEC) with and without TNF in clinically relevant doses. HUVEC were exposed to normothermia (37 degrees C) or moderate (39 degrees C) and severe (41 degrees C) HT for 90 or 180 min with or without TNF (1 microg/ml). Cell viability, cytokine secretion (IL-6, IL-8, VEGF, ICAM-1, VCAM-1, RANTES, E-selectin, P-selectin, L-selectin, and PECAM-1), and induction of procoagulant activity as reflected in tissue factor (TF) production were assessed at the end of the treatment period and at several time points thereafter. Neither HT nor TNF exerted significant cytotoxic effects on EC at the doses and temperatures used. HT resulted in increased production of PECAM-1 with little or no additional effect when combined with TNF. TNF caused increased secretion of IL-6, IL-8, ICAM-1, and VCAM-1 with little or no additional effect from HT. Increased E-selectin and RANTES levels were observed with TNF and HT only at 24 h after treatment. HT and TNF had mainly antagonistic effects on VEGF secretion with HT causing primarily decreased production and TNF causing increased VEGF secretion under all temperatures. Most notably, there was a rapid, prolonged and synergistic peak increase in procoagulant activity when TNF and HT were used in combination compared to TNF or HT treatment alone. These results indicate that TNF and HT exert primarily independent effects on inflammatory cytokine production in EC but synergistically increase procoagulant activity as reflected in TF production. These data provide a possible mechanism for the thrombotic effects in tumour neovasculature seen following isolation perfusion with these agents and provide a rationale for their combined use in this treatment setting.
机译：在肢体或肝脏的隔离灌注中应用高温（HT）和肿瘤坏死因子α（TNF）可导致大多数患者局限于体内这些区域的晚期癌症消退，并且据认为主要对以下部位产生抗肿瘤作用肿瘤新脉管系统。但是，尚不清楚哪种治疗因子对内皮细胞（EC）的单独贡献。在这项研究中，我们研究了中度和重度HT对临床相关剂量有无TNF的人脐静脉EC（HUVEC）的体外影响。将HUVEC暴露于常温（37摄氏度）或中度（39摄氏度）和严重（41摄氏度）的HT中，无论有无TNF（1 microg / ml），持续90分钟或180分钟。细胞活力，细胞因子分泌（IL-6，IL-8，VEGF，ICAM-1，VCAM-1，RANTES，E-选择素，P-选择素，L-选择素和PECAM-1）以及促凝血活性的诱导在治疗期结束时及其后的几个时间点评估组织因子（TF）产生中反映的数量。在使用的剂量和温度下，HT和TNF均未对EC产生明显的细胞毒性作用。与TNF结合使用时，HT导致PECAM-1的产量增加，几乎没有或没有其他作用。 TNF导致IL-6，IL-8，ICAM-1和VCAM-1的分泌增加，而HT几乎没有或没有其他作用。仅在治疗后24小时，TNF和HT观察到E-选择蛋白和RANTES水平升高。在所有温度下，HT和TNF对VEGF的分泌均具有主要的拮抗作用，其中HT引起的产量主要下降，而TNF则导致VEGF的分泌增加。最值得注意的是，与单独使用TNF或HT治疗相比，当将TNF和HT并用时，促凝活性迅速，持续且协同地出现峰值增加。这些结果表明，TNF和HT对EC中炎性细胞因子的产生起主要独立的作用，但协同增加促凝血活性，如TF产生所反映。这些数据提供了用这些药物隔离灌注后在肿瘤新脉管系统中观察到的血栓形成作用的可能机制，并为其在该治疗环境中联合使用提供了依据。

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