viscotoxin and Neoplasms

Mistletoe preparations, which are widely used among patients with cancer in Germany, have immunomodulating properties in vitro and in vivo. The aim of this evaluation was to determine and compare the effects of a lectin-rich (Iscador Qu [IQ] special, Weleda Company, Schwäbisch, Gmünd, Germany.) and a lectin-poor but viscotoxin-rich (Iscador Pini [IP] Weleda Company) mistletoe preparation on clinical and hematologic parameters in healthy subjects.. In a double-blinded study, 48 volunteers were randomized to one of three groups: 16 received IQ or IP in increasing doses or placebo twice per week subcutaneously for 12 weeks. The differential blood count and the acute phase markers haptoglobin and C-reactive protein were examined weekly and the symptoms were scored using standardized questionnaires.. IQ resulted in significant eosinophilia (315 +/- 109) beginning at week 5 (until week 12) compared to IP (183 +/- 120) or placebo (200 +/- 179). Furthermore, the acute phase marker haptoglobin was significantly increased in the IQ group during week 4. Dose-dependent local reactions (LRs) at the injection site occurred in all subjects who received mistletoe preparations but were stronger in the IQ-treated subjects than in the IP-treated group. The LRs observed in the IQ-treated group were characterized by stronger itching and longer latency than LRs in the IP-treated group (p < 0.05). Severe side-effects did not occur in any of the probands.. IQ but not IP can induce eosinophilia in healthy individuals, and this may be related to its content of mistletoe lectins. In contrast, exposure to the viscotoxin-enriched extract IP did not result in specific changes of hematologic parameters. Furthermore, intensity and time course of local reactions seemed to depend on the concentration of mistletoe lectins in those extracts.

Topics: Adjuvants, Immunologic; Adult; Antibody Formation; Biomarkers; Dose-Response Relationship, Drug; Double-Blind Method; Eosinophilia; Female; Humans; Male; Mistletoe; Neoplasms; Phytotherapy; Plant Lectins; Plant Preparations; Plant Proteins; Reference Values; Ribosome Inactivating Proteins, Type 2; Time Factors; Toxins, Biological; Treatment Outcome

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.. 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.. 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.. 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.

Topics: Adult; Antibody Formation; Double-Blind Method; Female; Humans; Immunoglobulin G; Immunoglobulin Isotypes; Lectins; Male; Mistletoe; Neoplasms; Phytotherapy; Plant Extracts; Plant Lectins; Plant Preparations; Plant Proteins; Ribosome Inactivating Proteins, Type 2; Toxins, Biological

Mistletoe extracts exert immunomodulatory properties on immunocompetent cells of the innate as well as the specific immune system. These effects have been mainly ascribed to mistletoe lectin 1 (ML-1) present in most of the extracts. However, it became evident that also other components of these extracts may induce immunological reactions, and especially viscotoxins (VT) may be of relevance. Aim of the study was, therefore, to evaluate whether VT like ML-1 could activate B-cells and lead to the production of VT-specific antibodies. Sera from 26 patients with different tumours who were treated with the mistletoe extract ABNOBAviscum Mali (AM) 4 for at least 18 weeks were analysed before therapy and after 3, 6, 9, 12, and 18 weeks. Sera were tested by ELISA against the four viscotoxins A1, A2, A3, B, as well as against ML-1. Within the observation period twenty-four (92%) of the 26 patients developed antibodies to at least one of the four VT and 25 (96%) to ML-1. In most instances, anti-VT antibodies appeared after 6-9 weeks of treatment. The antibodies were predominantly of the IgG type belonging preferentially to the IgG1 and IgG3 subclass. IgE antibodies were found only to VT-B and to ML-1. There was no relation between the development of antibodies to VT and ML-1, and also cross-reactivity could be excluded with high probability. These data indicate that not only ML-1 but also VT induce immunological responses in patients treated with mistletoe extracts. Whether there is any relationship to the postulated anti-tumour effect of mistletoe extracts has, however, still to be evaluated.

Topics: Adjuvants, Immunologic; Adult; Aged; Aged, 80 and over; Antibodies; B-Lymphocytes; Blotting, Western; Breast Neoplasms; Carcinoma, Renal Cell; Colonic Neoplasms; Enzyme-Linked Immunosorbent Assay; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Mistletoe; Neoplasms; Plant Preparations; Plant Proteins; Prostatic Neoplasms; Ribosome Inactivating Proteins, Type 2; Toxins, Biological

Lymphocytes of 25 patients treated with an aqueous mistletoe extract (Viscum album L.) for up to 6 months (group 1), up to 2 years (group 2), and more than 2 years (group 3) were examined in 3- and 7-day cultures for specifically sensitized lymphocytes. The whole extract (HM), the lectin-polysaccharide fraction (HM-LP), and the 'viscotoxin' fraction (HM-V) were added at concentrations ranging from 0.5 micrograms to 12.5 mg extract/ml. Lymphocytes from four of the nine group 2 patients and five of the ten group 3 patients reacted specifically with HM and HM-LP at an optimal dose of 5.0 mg/ml, but did not react with HM-V. Stimulation indices varied between 1.6 and 16. In the patients of group 3 this effect was observed only when their lymphocytes were co-stimulated in the 3-day cultures with phytohemagglutinin (PHA), in contrast to the four patients of group 2 who reacted only in the 7-day cultures with HM-LP without PHA co-stimulation. Patients' lymphocytes had to be protected from mistletoe lectin-induced cytotoxicity by the addition of their own sera containing anti-mistletoe lectin antibodies. Lymphocytes from tumor patients (n = 18) never treated with mistletoe extracts and healthy individuals (n = 18) showed no specific proliferative response when tested in 3- and 7-day cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Antibody Formation; Cells, Cultured; Dose-Response Relationship, Drug; Drug Administration Schedule; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interferon-gamma; Lymphocyte Activation; Neoplasms; Phytohemagglutinins; Plant Preparations; Plant Proteins; Polysaccharides; Ribosome Inactivating Proteins, Type 2; T-Lymphocytes; Toxins, Biological