Release of cytokines by a fermented lectin-1 (ML-1) free mistletoe extract reflects differences in the reactivity of PBMC in healthy and allergic individuals and tumour patients.

Abstract

Mistletoe extracts are used in adjuvant cancer treatment, but little is known concerning their mode of action. There is, however, evidence that antigens in these extracts may stimulate cells of the immune system, thereby modifying the altered immunological reactivity in tumour patients. In order to find out whether the postulated immunomodulatory properties of mistletoe extracts are mediated by cytokines, a spectrum of different cytokines was analysed in the supernatants of peripheral blood mononuclear cells (PBMC) from healthy (n = 23) and allergic (n = 16) individuals after stimulation with the fermented mistletoe lectin-1 (ML-1) free mistletoe extract Iscador Pini (IP) in vitro, and their cytokine patterns were compared to those from tumour patients with either breast cancer (n = 20) or colorectal tumours (n = 22). PBMC from healthy and allergic individuals produced high levels of TNF-alpha and IL-6 and to a lesser extent Th1- and Th2-related cytokines. This finding was in contrast to data obtained in tumour patients. Thus, the concentration of TNF-alpha was significantly lower in the cell cultures from breast cancer patients than in controls, and patients with colorectal tumours released IFN-gamma/IL-2 (5%) in the supernatants significantly less frequently than PBMC from healthy controls (26%). Similar results were obtained when the Th1- and monocyte/macrophage-related cytokines were analysed in the unstimulated cell cultures. These in vitro studies provide evidence that there is a reduced immunological reactivity to the fermented ML-1 free mistletoe extract in tumour patients and may give some clues as to how mistletoe-derived antigens could act on immune cells involved in the tumour defence.