Investigation of the effect of mistletoe (Viscum album L.) extract Iscador on the proliferation and apoptosis of murine thymocytes.
Mistletoe (Viscum album L.) extracts (ME) have been shown to exhibit a bell-shaped curve of immunological efficacy and mistletoe lectins (MLs) were found to play an important role in this phenomenon. The aim of present in vivo study was to investigate the acute- and long-term effect of a standardized ME (Iscador M special) on thymocyte subpopulations and peripheral T cells using a murine (Balb/c) model. In thymus CD4-CD8- double negative (DN), CD4+CD8+ double positive (DP), CD4+ or CD8+ single positive T cells were determined 24 h after a single injection or following a long-term treatment (twice a week for 4 weeks) with three different dilutions of ME which are corresponding to 4.5 ng/ kg, 22.5 ng/kg and 112.5 ng/kg doses of MLs. The apoptosis of the thymocytes was also tested by flow cytometry using Annexin V and propidium iodide. 24 h after a single injection of ME only the lowest dose caused in the blood samples an elevated CD4+/CD8+ ratio and in thymus an enhanced proliferation of DN thymocytes indicating a similar bell-shaped curve of immunological efficacy. After a treatment for four weeks these responses were less intensive indicating that none of the three doses are immunologically optimal. Surprisingly, both in the acute and in the long-term trial only the lower doses induced significant enhancements in the ratio of apoptotic thymocytes. In addition, ME inhibited the dexamethasone (DX)-induced reduction of DN cell count in thymus, as well as the DX-induced decrease of CD4+/CD8+ ratio and CD4+ cell level in peripheral blood. These in vivo results suggest that investigation of thymocytes in vivo can be helpful in the immunological dose-finding since standardized ME is able to modulate the proliferation and apoptosis of thymocytes with a bell-shaped curve of efficacy. In addition, ME may act lymphoprotectively during DX treatment.
Hajtò
Tibor
T
Department of Immunology and Biotechnology, University of Pécs, Faculty of Medicine, Pécs, Hungary. drhajtot@axelero.hu
Berki
Timea
T
Pàlinkàs
Làszlò
L
Boldizsàr
Ferenc
F
Németh
Péter
P
D000276:Adjuvants, Immunologic; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016516:CD4-CD8 Ratio; D002452:Cell Count; D049109:Cell Proliferation / Q000187:drug effects*; D003907:Dexamethasone / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D005260:Female; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000494:pharmacology*; D010940:Plant Proteins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects
D000276:Adjuvants, Immunologic; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D010940:Plant Proteins; D003907:Dexamethasone; C077177:viscum album peptide