Huber R, Barth H, Schmitt-Gräff A, Klein R
Center for Complementary Medicine, Department of Gastroenterology, University of Freiburg, Germany.
J Altern Complement Med. 2000 Aug;6(4):305-10. doi: 10.1089/10755530050120664.
A patient with inoperable adenocarcinoma of the pancreas was treated with intraperitumoral and peritumoral injections of a Viscum album L. extract containing 5,700 ng/mL mistletoe lectin, mainly mistletoe lectin 1 (Abnobaviscum Quercus 2) for 5 weeks (1 injection per week). After the third injection (day 22), a marked eosinophilia was observed (1,800 per microliter) that rose to 3,268 per microliter after the fifth injection (day 42). Furthermore, histology performed on day 28 revealed accumulation of eosinophils in ductal lesions and adjacent stroma in addition to the features of ductal adenocarcinoma. In order to investigate whether eosinophilia correlated with immunological features, we analyzed cytokine production of peripheral blood mononuclear cells (PBMC) from this patient after stimulation with antigens known to "unmask" an individual's predisposition for defined immunoreactions, namely purified protein derivative (PPD) as a stimulator of T-helper (TH1)1-cells and tetanus toxoid (TT) as an activator of TH2-cells. PBMC of the patient showed a strong proliferation and production of interleukin (IL)-5 and IL-10 after incubation with TT indicating a type-2 response. Simultaneously, PBMC were induced to proliferate and produce interferon gamma (IFN-gamma) by incubation with PPD suggesting also a type-1 response. These data would readily explain the eosinophilia because eosinophils are effector cells of type-2 reaction but also require type-1 cytokines. Although the overall clinical course of the patient was rapidly progressive, temporary stabilization of the patient's general condition during mistletoe treatment was observed. It is, however, still an open question whether this transient benefit was due to the induction of eosinophilia by a type-2 response.
Before high-dose intratumoral and peritumoral treatment with a Viscum album L. extract containing mistletoe, lectin 1 can be associated with hypereosinophilia and strong production of TH1 as TH2 cytokines as well.
一名患有无法手术切除的胰腺腺癌患者接受了瘤内和瘤周注射含有5700 ng/mL槲寄生凝集素(主要是槲寄生凝集素1,Abnobaviscum Quercus 2)的欧洲槲寄生提取物治疗,为期5周(每周注射1次)。第三次注射后(第22天),观察到明显的嗜酸性粒细胞增多(每微升1800个),第五次注射后(第42天)升至每微升3268个。此外,第28天进行的组织学检查显示,除了导管腺癌的特征外,在导管病变和相邻基质中还存在嗜酸性粒细胞聚集。为了研究嗜酸性粒细胞增多是否与免疫特征相关,我们分析了该患者外周血单个核细胞(PBMC)在用已知可“揭示”个体对特定免疫反应易感性的抗原刺激后的细胞因子产生情况,即作为T辅助(TH1)1细胞刺激剂的纯化蛋白衍生物(PPD)和作为TH2细胞激活剂的破伤风类毒素(TT)。患者的PBMC在与TT孵育后显示出强烈的增殖以及白细胞介素(IL)-5和IL-10的产生,表明为2型反应。同时,PBMC在与PPD孵育后被诱导增殖并产生干扰素γ(IFN-γ),这也表明为1型反应。这些数据很容易解释嗜酸性粒细胞增多的原因,因为嗜酸性粒细胞是2型反应的效应细胞,但也需要1型细胞因子。尽管患者的总体临床病程进展迅速,但在槲寄生治疗期间观察到患者的一般状况有暂时稳定。然而,这种短暂的益处是否归因于2型反应诱导的嗜酸性粒细胞增多仍是一个悬而未决的问题。
在用含有槲寄生凝集素1的欧洲槲寄生提取物进行高剂量瘤内和瘤周治疗之前,可能会出现嗜酸性粒细胞增多以及TH1和TH2细胞因子的大量产生。