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癌症患者局部白细胞介素-2治疗期间细胞因子谱的变化。

Changes in cytokine profile during local IL-2 therapy in cancer patients.

作者信息

Tomova Radosveta, Pomakov Javor, Jacobs John J L, Adjarov Dimcho, Popova Svetlana, Altankova Iskra, Den Otter Willem, Krastev Zachary

机构信息

Clinic of Gastroenterology, University Hospital "St.Ivan Rilski", #15, Blvd. "Iv.Geshov", Sofia 1431, Bulgaria.

出版信息

Anticancer Res. 2006 May-Jun;26(3A):2037-47.

Abstract

BACKGROUND

Exogenous interleukin 2 (IL-2) can influence the complex cytokine network in vivo. This study investigated the cytokine profile of patients with different malignancies before and after local IL-2 administration.

PATIENTS AND METHODS

The human TH1 / TH2 cytometric bead array (CBA) kit was used to investigate IL-2, IFNgamma, TNFalpha, IL-4, IL-5 and IL-10 in a control group and in 13 patients.

RESULTS

The baseline serum IL-4 levels in patients were lower than in healthy controls, while the baseline ascitic IL-10 levels in patients was higher than in serum. The IL-2 applications induced a strong serum increase in IL-2 and IL-5 and even more in ascites, while IL-10 increased weakly and mainly locally. One month after the start of therapy, the serum IFNgamma had increased in patients, reaching the level of the control group.

CONCLUSION

After local injection, IL-2 probably leaks into the blood circulation. The higher increases of IL-2, IL-5 and IL-10 in ascites compared to the serum suggests that the injected cytokines and their effects are mainly local. The minor increase of the immunosuppressive IL-10 could explain the therapeutic difference between local and systemic IL-2 therapy since IL-10 levels markedly increase after systemic IL-2 therapy. IL-5 was always increased after IL-2 therapy and, consequently, may be a downstream mediator of antitumour responses.

摘要

背景

外源性白细胞介素2(IL-2)可影响体内复杂的细胞因子网络。本研究调查了不同恶性肿瘤患者局部注射IL-2前后的细胞因子谱。

患者与方法

使用人TH1/TH2细胞计数珠阵列(CBA)试剂盒检测13例患者及一个对照组中的IL-2、干扰素γ(IFNγ)、肿瘤坏死因子α(TNFα)、IL-4、IL-5和IL-10。

结果

患者的基线血清IL-4水平低于健康对照组,而患者的基线腹水IL-10水平高于血清。IL-2注射导致血清中IL-2和IL-5显著升高,腹水中升高更明显,而IL-10仅轻微升高且主要是局部升高。治疗开始1个月后,患者血清IFNγ升高,达到对照组水平。

结论

局部注射后,IL-2可能漏入血液循环。与血清相比,腹水中IL-2、IL-5和IL-10升高幅度更大,表明注射的细胞因子及其作用主要在局部。免疫抑制性IL-10的轻微升高可能解释了局部和全身IL-2治疗的差异,因为全身注射IL-2后IL-10水平会显著升高。IL-2治疗后IL-5总是升高,因此,它可能是抗肿瘤反应的下游介质。

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