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Toxic proteins from European mistletoe (Viscum album L.): increase of intracellular IL-4 but decrease of IFN-gamma in
G M Stein1, U Pfüller, M Schietzel
1Krebsforschung Herdecke, Department of Applied Immunology, University Witten/Herdecke, Communal Hospital, Germany. stein.g@debitel.net
Anticancer Research
|August 6, 2000
Summary
Mistletoe lectins (ML) induce apoptosis and increase Interleukin-4 (IL-4) in T-cells, primarily in dying cells. This suggests IL-4 plays a role in apoptosis beyond T-helper cell activation.
Area of Science:
- Immunology
- Cancer Therapy
Background:
- Mistletoe lectins (ML) are key components of mistletoe extracts used in cancer therapy.
- ML induce apoptosis in lymphocytes and tumor cells.
- The role of dying versus activated cells in cytokine release upon ML exposure is unclear.
Purpose of the Study:
- To investigate the role of ML and viscotoxins (VT) in cytokine production and apoptosis.
- To determine if IL-4 expression is linked to apoptosis or necrosis induced by ML.
Main Methods:
- Flow cytometry was used to analyze IFN-gamma, IL-4, Apo2.7 (apoptosis marker), and Bcl-2 protein expression.
- Peripheral blood mononuclear cells (PBMC) from controls and plasmocytoma cells (U-266) were treated with ML or VT.
Main Results:
- ML inhibited IFN-gamma production but increased IL-4 expression in CD8+ and CD4+ T-cells.
- IL-4 was predominantly found in apoptotic cells with low Bcl-2 levels.
- VT induced cell membrane permeabilization and Bcl-2 loss but not IL-4 production, indicating IL-4 is linked to apoptosis, not necrosis.
Conclusions:
- IL-4 expression is associated with apoptosis induced by mistletoe lectins.
- IL-4 may have an important, yet undefined, role in the apoptosis of normal and tumor cells.
- These findings contribute to understanding the mechanisms of mistletoe extract in cancer therapy.