Intracellular expression of IL-4 and inhibition of IFN-γ by extracts from European mistletoe is related to induction of apoptosis

Background: Extracts from European mistletoe are used for adjuvant cancer treatment. Their influence on the intracellular expression of cytokines of the T-helper cells type-1 (Th1; IFN-gamma) or type-2 (Th2; IL-4) is still unknown. Materials and Methods: Lymphocytes fi om controls were incubated with mistletoe extracts (ME) and mistletoe lectins (ML) for 24 hours and co-stimulated with PMA/Ca-ionophore/monensin during the last 6 hours. Apoptosis and intracellular cytokine expression were detected by flow cytometry, the cytokine release into the supernatants by ELISA. Results: ME and ML significantly inhibited intracellular expression of IFN-gamma but stimulated IL-4. Thereby, IL-4 was mainly expressed in apoptotic (Apo2.7(+)) cells. However, IFN-gamma secretion into the supernatants of the cells was dose-dependently inhibited by ME and ML, while IL-4 was not detected at all. Conclusion: The intracellular expression of the 'Th2-cytokine' IL-4 in ME- and ML-exposed cells may not be related to a typical Th2-response bur rather to cell death. This effect might be of great relevance e.g. after intratumoural injection of the mistletoe extracts and, in general, for the inhibition of an inflammatory response during apoptosis.