Heinzerling Lucie, von Baehr Volker, Liebenthal Christa, von Baehr Rüdiger, Volk Hans-Dieter
Department of Medical Immunology, Charité - University Hospital, Berlin, Germany.
J Clin Immunol. 2006 Jul;26(4):347-59. doi: 10.1007/s10875-006-9023-5. Epub 2006 May 17.
Even though mistletoe extracts have been in clinical use for centuries their exact mode of action is still unknown. Currently, the application scheme for registered preparations is a dose-escalating scheme to thus reduce side effects. In this study, healthy controls and patients were evaluated for their immunologic response to treatment with a standardized mistletoe extract (Iscador). It shows a strong effect as adjuvant that induces TNF-alpha and IL-12, which was partly mediated via CD14. Desensitization of the TNF-alpha response could be shown after repeated application in vitro and in vivo. Furthermore, Iscador induces a specific lymphocyte sensitization upon multiple injections and production of IgG1- and IgG3 -mistletoe antibodies. Remarkably, a systemic bystander effect (heterologous immunity against other recall antigens) was observed after long-term treatment. In conclusion, dose-escalation reduces the monocyte-related clinical side effects. A T-lymphocyte sensitization stimulates mainly a specific Th1 response. The most interesting clinical long-term effect is the bystander stimulation of various memory T cells that might mediate in vivo antitumor and antiinfectious T-cell response under mistletoe-extract immunization.
尽管槲寄生提取物已在临床应用了几个世纪，但其确切的作用方式仍然未知。目前，已注册制剂的应用方案是一种剂量递增方案，以减少副作用。在本研究中，对健康对照者和患者进行了评估，以了解他们对标准化槲寄生提取物（Iscador）治疗的免疫反应。它作为佐剂显示出强大的作用，可诱导肿瘤坏死因子-α（TNF-α）和白细胞介素-12（IL-12），部分是通过CD14介导的。在体外和体内重复应用后，可显示TNF-α反应的脱敏现象。此外，Iscador在多次注射后可诱导特异性淋巴细胞致敏，并产生IgG1和IgG3槲寄生抗体。值得注意的是，长期治疗后观察到一种全身性旁观者效应（针对其他回忆抗原的异源免疫）。总之，剂量递增可减少与单核细胞相关的临床副作用。T淋巴细胞致敏主要刺激特异性Th1反应。最有趣的临床长期效应是对各种记忆T细胞的旁观者刺激，这可能在槲寄生提取物免疫下介导体内抗肿瘤和抗感染T细胞反应。
