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Immunologic Effector Mechanisms of a Standardized Mistletoe Extract on the Function of Human Monocytes and Lymphocytes in vitro, ex vivo, and in vivo

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Abstract

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-α and IL-12, which was partly mediated via CD14. Desensitization of the TNF-α 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.

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Abbreviations

IL:

interleukin

IFN:

interferon

TNF:

tumor necrosis factor

Ig:

Immunoglobulin

ML:

mistletoe lectin

Qu:

Quercus

Da:

Dalton

PBMC:

peripheral blood mononuclear cells

SI:

stimulation index

LTT:

lymphocyte transformation test

APC:

antigen presenting cell.

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ACKNOWLEDGMENTS

We thank Prof. R. Gorter for his support in this study, Dr. Stein for the evaluation of IgG mistletoe antibodies and the Hiscia for donating the mistletoe extract, and Dr. Franziska Loeper for her assistance in getting clinical data. The study was partly financed by the Institute for Clinical Research, Berlin, Germany.

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Authors and Affiliations

  1. Department of Medical Immunology, Charité – University Hospital, Berlin, Germany

    Lucie Heinzerling, Volker Von Baehr, Christa Liebenthal & Hans-Dieter Volk

  2. Institute for Medical Diagnostic, Berlin, Germany

    Volker Von Baehr & RÜdiger Von Baehr

  3. Department of Dermatology and Allergy, Charité – University Hospital, Schumannstrasse 20/21, 10117, Berlin, Germany

    Lucie Heinzerling

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  1. Lucie Heinzerling
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  2. Volker Von Baehr
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  5. Hans-Dieter Volk
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Correspondence to Lucie Heinzerling.

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Heinzerling, L., Von Baehr, V., Liebenthal, C. et al. Immunologic Effector Mechanisms of a Standardized Mistletoe Extract on the Function of Human Monocytes and Lymphocytes in vitro, ex vivo, and in vivo . J Clin Immunol 26, 347–359 (2006). https://doi.org/10.1007/s10875-006-9023-5

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  • DOI: https://doi.org/10.1007/s10875-006-9023-5

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