Pharmacological perspectives of mistletoe therapy

T Hajto

Hungarian Immune Therapy Health and Service Deposit Partnership, H-1075 Budapest, Hungary

Concerning both cytostatic/apoptotic and immunomodulatory effects of mistletoe plant extracts always more data suggest the pharmacological importance of a lectin, Viscum album agglutinin (VAA)-I based on a number of in vitro and in vivo experiments. The cytostatic/apoptotic effects of VAA-I in culture of various eukaryotic cells were tested by flow cytometry with propidium iodide (PI) and with terminal deoxynucleotydil transferase (TdT)-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay. The cytokine/hematopoetic growth factor ? inducing/enhancing effects of VAA-I in 24h culture of human peripheral mononuclear cells (PBMC) or 14 days culture of CD34+ bone marrow cells with enzyme linked immunosorbit assay (ELISA), reverse polymerase chain reaction (rPCR) or by assessment of clonogenic growth were investigated. The natural killer (NK) cytotoxic activity of animal splenocytes and of human PBMC (in vitro and ex vivo) was against YAC-1 and K562 target cells tested, respectively. In 24h culture of eukaryotic cells VAA-I has been shown to induce cytostatic effects above 10 ng/ml and a dose-dependent apoptosis between 10 ng/ml and 1 mg/ml concentration. After 24h incubation of human PBMC, VAA-I induced mRNA expression and enhanced secretion of proinflammatory cytokines. Both in vitro and in vivo VAA-I stimulated the number and activity of NK cells. In addition, VAA-I induced elevated effect of hematopoietic growth factors on CD34+ bone marrow cells. Studies in animal models suggest that application of 0.5-3 ng VAA-I/kg twice a week is effective on elevated cellular activity of natural immune system. These results suggest a potential use of VAA-I as an immunomodulator which is also able to manipulate the balance between cell growth and programmed cell death.

KEY WORDS: Viscum album agglutinin, apoptosis, immunomodulation.

Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Novel Therapies, Part 1.