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

Background: Extracts from European mistletoe are used for adjuvant cancer t reatment. Their influence on the intracellular expression of cytokines of t he T-helper cells type-1 (Th1; IFN-gamma) or type-2 (Th2; IL-4) is still un known. Materials and Methods: Lymphocytes fi om controls were incubated wit h mistletoe extracts (ME) and mistletoe lectins (ML) for 24 hours and co-st imulated 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 signifi cantly 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-dependent ly 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-expos ed cells may not be related to a typical Th2-response bur rather to cell de ath. This effect might be of great relevance e.g. after intratumoural injec tion of the mistletoe extracts and, in general, for the inhibition of an in flammatory response during apoptosis.