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

Background: 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 apoptosis-inducing effects. This study investigates the acute and long-term effects of standardized mistletoe extract (Iscador(R) M spec 5 mg) on thymocyte subpopulations and peripheral T-cells using a murine (Balb/c) model. Materials and Methods: 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. Results: 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. Conclusion: 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.