Tomova Radosveta, Pomakov Javor, Jacobs John J L, Adjarov Dimcho, Popova Svetlana, Altankova Iskra, Den Otter Willem, Krastev Zachary
Clinic of Gastroenterology, University Hospital "St.Ivan Rilski", #15, Blvd. "Iv.Geshov", Sofia 1431, Bulgaria.
Anticancer Res. 2006 May-Jun;26(3A):2037-47.
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.
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.
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.
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.
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。
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。
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。
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。