Effects of mistletoe extract on murine thymocytes in vivo and on glucocorticoid-induced cell count reduction

Mistletoe extracts are widely used in cancer patients due to their cytostatic and immunomodulatory effects. Essential components include mistletoe lectins which act as biomodulators with proinflammatory and apoptosisinducing effects. This study investigates the acute and longterm effects of standardized mistletoe extract (Iscador(R) M spec 5 mg) on thymocyte subpopulations and peripheral T-cells using a murine (Balb/c) model.

Using cell surface CD4/CD8 staining and flow cytometry, we followed the changes in CD4-CD8- double-negative (DN), CD4(+)CD8(+) double-positive (DP) and CD4(+) or CD8(+) single-positive (SP) T-cells 24 h after single or repeated injections of 3 different dilutions (1:12, 1:60, 1:300) corresponding to 2.1, 0.42 and 0.08 mg/kg of Iscador. Thymocyte apoptosis was detected by flow cytometry using Annexin V and propidium iodide.

24 h after a single injection of the 2 lower doses, the number of DN thymocytes increased significantly with an enhanced ratio of apoptotic cells. Following administration of the lowest dose, in peripheral blood the CD4(+)/CD8(+) ratio was elevated. In the long-term trial, Balb/c mice were treated twice a week with 3 different doses of Iscador +/- 20 mg/kg of dexamethasone (DX), resulting in significantly enhanced DN thymocytes and elevated levels of apoptotic cells after treatment with the 2 lower doses. Iscador also inhibited the DX-induced reduction in the thymic DN cell count, as well as the DX-induced decrease in the CD4(+)/CD8(+) ratio and CD4(+) in the peripheral blood.

Our results suggest that standardized mistletoe extract modulates proliferation and apoptosis of thymocytes in a dose-dependent manner and may act lymphoprotective during DX treatment.