title: Immunologic effector mechanisms of a standardized mistletoe extract on the function of human monocytes and lymphocytes in vitro, ex vivo, and in vivo.
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-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.
authors.affiliation: Department of Medical Immunology, Charité - University Hospital, Berlin, Germany. lucie.heinzerling@charite.de
authors.forename: Lucie
authors.initials: L
authors.lastname: Heinzerling
authors.forename: Volker
authors.initials: V
authors.lastname: von Baehr
authors.forename: Christa
authors.initials: C
authors.lastname: Liebenthal
authors.forename: Rüdiger
authors.initials: R
authors.lastname: von Baehr
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
mesh_terms: 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
chemical_list: D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D010936:Plant Extracts; D010940:Plant Proteins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; C077177:viscum album peptide