In vivo-induction of antibodies to mistletoe lectin-1 and viscotoxin by exposure to aqueous mistletoe extracts: a randomised double-blinded placebo controlled phase I study in healthy individuals.
BACKGROUND
Several studies have been performed in tumour patients to analyse the immunological response to mistletoe extracts. Considering the fact that these extracts are given subcutaneously in most instances, the kind of application resembles a typical immunization schedule. We therefore wanted to see how those extracts act on immunocompetent cells of healthy individuals hoping that this kind of provocation test may give new informations about a more specific application of these extracts in certain diseases.


METHODS
47 healthy individuals were exposed for twelve weeks either to Iscador Quercus special (IQ) known to be rich in mistletoe lectin (ML)-1 (n = 16), to Iscador Pini (IP) being poor in ML-1 but enriched in viscotoxins (n = 15), or to placebo (physiological saline) (n = 16) in a randomised, double-blinded placebo-controlled study. Humoral immunoreactivity was analysed by measuring antibodies towards the two compounds ML-1 and viscotoxin VA2 (VA2). Sera were collected in intervals of four weeks up to week 12 and again three months after last exposure.


RESULTS
None of the subjects had antibodies to ML-1 or VA2 before exposure. In week 12, anti-ML-1 antibodies of the IgG-type were found in all 16 IQ-treated individuals but only 6 of the 15 probands exposed to IP. In contrast, anti-VA2 IgG-antibodies could be detected in all individuals of both groups. The antibodies were preferentially of the IgG1 and IgG3 type while antibodies of the IgA and IgM type were produced only in a few probands. Antibodies of the IgE-type occurred only in the IQ-exposed individuals and were directed against ML-1 but not VA2. None of the probands receiving placebo developed antibodies to ML-1 or VA2. Severe side effects were not observed in any of the probands.


CONCLUSIONS
These data obtained in healthy individuals clearly indicate that IQ and IP-extracts can induce antigen-specific humoral responses. They may, therefore, provide, a solid basic for the evaluation of the humoral immune response in disease states.
Klein
R
R
Department of Internal Medicine II, University of Tübingen, Germany. reinhild.klein@med.uni-tuebingen.de
Classen
K
K
Berg
P A
PA
Lüdtke
R
R
Werner
M
M
Huber
R
R
D000328:Adult; D000917:Antibody Formation; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis; D037102:Lectins / Q000008:administration & dosage* / Q000276:immunology* / Q000302:isolation & purification; D008297:Male; D014784:Mistletoe / Q000276:immunology*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000008:administration & dosage* / Q000276:immunology* / Q000302:isolation & purification
D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D037102:Lectins; D010936:Plant Extracts; D037121:Plant Lectins; D028321:Plant Preparations; D010940:Plant Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C009674:ribosome inactivating protein, Viscum; C488038:viscotoxin