AViscum album oligosaccharide activating human natural cytotoxicity is an interferon γ inducer

Abstract

Commercial Viscum album extract Helixor-M contains a dialysable oligosaccharide (HM-BP) that activates natural killer (NK) cytotoxicity against K562 tumour cells when preincubated with human peripheral blood mononuclear cells (PBMC) for 72 h. The activated effector cells were exclusively found in the monocyte/macrophage subpopulation. However, when peripheral non-adherent cells (PNAC) were preincubated with HM-BP for 72 h the NK cytotoxicity of CD56+CD3- NK cells was activated. This discrepancy was found to be due to the release of prostaglandin E2 from activated monocytes/macrophages, which blocked activation of the cytotoxicity of NK cells. Analysis of the supernatant culture medium after 72 h preincubation demonstrated that HM-BP induced release of interferon gamma (IFN gamma) from T cells (preferentially from CD3+CD4+ cells) and of tumour necrosis factor alpha (TNF alpha) from monocytes/macrophages. Release of IFN gamma was the crucial step for activation of NK cytotoxicity since enhancement of NK cytotoxicity during pretreatment of PBMC or PNAC with HM-BP was completely blocked in the presence of anti-IFN gamma antibodies. Anti-interleukin-2, anti-TNF alpha or anti-IFN alpha antibodies had no effect on the HM-BP-induced enhancement of NK cytotoxicity. The activation of the NK cytotoxicity of nonadherent cells by interleukin-2 treatment was found to be synergistic to the enhancement of NK cytotoxicity by treatment with HM-BP.

Variable Sensitivity of Lymphoblastoid Cells to Apoptosis Induced by <i>Viscum album</i> Qu FrF, a Therapeutic Preparation of Mistletoe Lectin

“…Studies with the isolated individual components of mistletoe extracts are useful in understanding the molecular mechanisms underlying the beneficial effect of the therapeutic preparation. Such studies are, however, at times misleading, as they do not take into account the additive effect, whether positive or negative, of different components in the final preparation [34][35][36][37]. Another critical question concerning studies with individual purified components relates to the issue of the concentration of lectins used in in vitro studies.…”

No Evidence of IFN-γ Increase in the Serum of HIV-Positive and Healthy Subjects after Subcutaneous Injection of a Non-Fermented <i>Viscum album</i> L. Extract

“…The storage of samples at 4°C or room temperature between the time of sampling and the time of measurement has no effect on the results [30]. As the first increase in IFN-Á occurs in vitro in PBMC after incubation with V. album L. after 24 h and is detectable over the following 5 days [14], sampling at a time point 24-27 h after the last injection should have been appropriate to detect any increases in serum concentrations. As the half-life of IFN-Á in serum is 5 h to 2 days [18,19], our design should have been suitable for the detection of any increase in levels, as accumulation should have occurred after repeated injections at intervals of 3-4 days.…”

“…For up to 12 h, the concentration of IFN-Á in the culture medium was identical to that for PBMC incubated without V. album L. extract. Subsequently, there was a rapid increase in IFN-Á levels up to the time point of 72 h, followed by a slow fall back in the rate, but levels of IFN-Á were still increased after 120 h [14]. Twenty-four hours after in vitro stimulation with phytohaemagglutinin (PHA) and mistletoe lectin of PBMCs obtained from cancer patients who had received V. album L. extract over 2 years, no stimulation of IFN-Á was reported [15].…”

“…According to Müller and Anderer [14], IFN-Á is primarily released by monocytes and CD8+ lymphocytes after incubation with V. album L. There is a clear time dependency of IFN-Á release from PBMCs. For up to 12 h, the concentration of IFN-Á in the culture medium was identical to that for PBMC incubated without V. album L. extract.…”

Effects of Mistletoe Extract on Murine Thymocytes in vivo and on Glucocorticoid-Induced Cell Count Reduction

“…This may be the reason why, for the last 14 years, research of mistletoe extracts mainly focused on lectins. Other substances of plant extracts, such as viscotoxins [3,4], poly-and oligosaccharides [5], flavonoids [6,7], membrane lipids [8] and arginin [9], have also been discussed in connection with the effects of mistletoe extracts on the host defense. So far, however, little evidence has been found for the contribution of these substances to the effects of mistletoe in vivo.…”