Immunologic effector mechanisms of a standardized mistletoe extract on the function of human monocytes and lymphocytes in vitro, ex vivo, and in vivo.
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.
Heinzerling
Lucie
L
Department of Medical Immunology, Charité - University Hospital, Berlin, Germany. lucie.heinzerling@charite.de
von Baehr
Volker
V
Liebenthal
Christa
C
von Baehr
Rüdiger
R
Volk
Hans-Dieter
HD
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000187:drug effects*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology / Q000494:pharmacology; D024201:Bystander Effect; D016022:Case-Control Studies; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007114:Immunization; D018664:Interleukin-12 / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects*; D008875:Middle Aged; D014784:Mistletoe / Q000276:immunology; D009000:Monocytes / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy; D010936:Plant Extracts / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D010940:Plant Proteins / Q000008:administration & dosage* / Q000276:immunology / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000235:genetics; D002578:Uterine Cervical Dysplasia / Q000188:drug therapy
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D010936:Plant Extracts; D010940:Plant Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C077177:viscum album peptide