Elsässer-Beile U, Lusebrink S, Grussenmeyer T, Wetterauer U, Schultze-Seemann W
Department of Urology, University of Freiburg, Germany.
Arzneimittelforschung. 1998 Dec;48(12):1185-9.
The aim of the present study was to compare the biological effects of 12 different clinically applied mistletoe preparations (I, II, III and IV) from the host trees "pinus" (P), "malus" (M), "abies" (A) and "quercus" (Q) on human leukocytes. When the preparations I-P, II-P, III-P and IV-A were added to the whole blood cell cultures of 37 cancer patients (breast cancer, n = 22, colorectal cancer, n = 15) and 34 healthy controls, a significant induction of the cytokines IL-1-beta, IL-2, IL-6, IL-10 and TNF-alpha was found with preparation I-P. A significant induction of IL-1-beta and TNF-alpha was obtained with the preparations II-P and III-P as compared to the nonstimulated control cultures. Induction of IFN-gamma was not found with any preparation. Cytokine induction was comparable in the blood cell cultures of the tumor patients and the healthy controls. When the clinical preparations I-P, I-M, I-Q, II-P, II-M, II-A, III-P, III-M, III-A and IV-P, IV-M, IV-A were tested in cultures of peripheral blood mononuclear cells from 5 healthy donors, differences in the induction of cytokine production and apoptosis were seen after addition of the mistletoe preparations from different host trees. Increased levels of IL-1-beta were found after addition of the preparations I-P and I-M, increased levels of TNF-alpha were measured after addition of preparations I-P and III-A. Induction of apoptosis was most evident with the preparations I-M, I-Q, III-M and IV-A. Neither cytokine induction nor apoptosis could be correlated to the amount of lectins found in the preparations. Stimulation of separated CD4(+)-, CD8(+)- and CD14(+)-cells from 5 healthy donors with the above noted preparations revealed an induction of IL-1-beta and TNF-alpha production by the preparations I-P, I-M and I-Q mainly in monocytes and to a minimal extent in lymphocytes. Also apoptosis was seen mainly in CD14(+)-monocytes. From these results it is concluded that both, apoptosis and cytokine production are induced differentially in leukocyte cultures by clinically applied mistletoe preparations. However, there is no correlation between the biological effects and the lectin content of the various preparations and none of them were comparable with respect to the extent of these effects. Therefore, it may be expected that clinical studies with different preparations are not comparable either.
本研究的目的是比较12种临床上应用的来自寄主树“松树”（P）、“苹果树”（M）、“冷杉”（A）和“栎树”（Q）的不同槲寄生制剂（I、II、III和IV）对人白细胞的生物学效应。当将制剂I-P、II-P、III-P和IV-A添加到37名癌症患者（乳腺癌，n = 22；结直肠癌，n = 15）和34名健康对照者的全血细胞培养物中时，发现制剂I-P能显著诱导细胞因子IL-1-β、IL-2、IL-6、IL-10和TNF-α。与未刺激的对照培养物相比，制剂II-P和III-P能显著诱导IL-1-β和TNF-α。任何制剂均未发现诱导IFN-γ。肿瘤患者和健康对照者的血细胞培养物中的细胞因子诱导情况相当。当对来自5名健康供体的外周血单核细胞培养物进行临床制剂I-P、I-M、I-Q、II-P、II-M、II-A、III-P、III-M、III-A以及IV-P、IV-M、IV-A的测试时，添加来自不同寄主树的槲寄生制剂后，在细胞因子产生诱导和凋亡方面存在差异。添加制剂I-P和I-M后发现IL-1-β水平升高，添加制剂I-P和III-A后测量到TNF-α水平升高。制剂I-M、I-Q、III-M和IV-A诱导凋亡最为明显。细胞因子诱导和凋亡均与制剂中发现的凝集素量无关。用上述制剂刺激5名健康供体分离的CD4(+)、CD8(+)和CD14(+)细胞，发现制剂I-P、I-M和I-Q主要在单核细胞中诱导IL-1-β和TNF-α产生，在淋巴细胞中诱导程度最小。凋亡也主要出现在CD14(+)单核细胞中。从这些结果可以得出结论，临床上应用的槲寄生制剂在白细胞培养物中对凋亡和细胞因子产生的诱导存在差异。然而，生物学效应与各种制剂的凝集素含量之间没有相关性，并且就这些效应的程度而言，它们之间没有可比性。因此，可以预期不同制剂的临床研究也不可比。
