Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Weissert, R; Wiendl, H; Pfrommer, H; Storch, MK; Schreiner, B; Barth, S; Seifert, T; Melms, A; Dichgans, J; Weller, M.
Action of treosulfan in myelin-oligodendrocyte-glycoprotein-induced experimental autoimmune encephalomyelitis and human lymphocytes.
J NEUROIMMUNOL 2003 144: 28-37.
Doi: 10.1016%2Fj.jneuroim.2003.08.028
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- Co-Autor*innen der Med Uni Graz
- Seifert-Held Thomas
- Storch Maria
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- Abstract:
- Treosulfan (dihydroxybusulfane, DHB, L-threitol-1,4-bis [methane sulfonate]) is a cytostatic alkylating agent with a favorable profile of side effects. Myelin-oligodendrocyte-glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE) induced in DA (RT1(av1)) rats resembles multiple sclerosis (MS) in many aspects since central nervous system (CNS) pathology shows inflammation, demyelination and axonal loss. Moreover, DA rats develop a chronic disease course. We here explored the efficacy of treosulfan in the treatment of MOG-induced EAE in DA rats. A single dose of treosulfan (1 g/kg body weight i.p.) at the day of immunization significantly reduced disease severity compared with PBS-treated controls. In addition, after disease had evolved, a single dose of treosulfan (1 g/kg body weight) given i.p. on day 14 post-immunization (p.i.) improved long-term disease outcome. Treatment with treosulfan resulted in reduced mRNA expression of IL-12 and interferon (IFN)-gamma in draining lymph nodes and reduced numbers of IFN-gamma-secreting MOG-specific T cells. No myelosuppression was observed. Treosulfan was applied to different subsets of cultured human blood mononuclear cells in order to asses the effects on human immune cells in vitro: Treosulfan reduced proliferative capacity and increased apoptosis in T cells and antigen-presenting cells. In light of the beneficial effects in EAE in vivo and the in vitro immunosuppressive and pro-apoptotic capacities in cultured human mononuclear immune effector cells, these data may support a potential role of treosulfan, an agent with high immunosuppressive capacity and low toxicity, in the treatment of MS.
- Find related publications in this database (using NLM MeSH Indexing)
- Amino Acid Sequence -
- Animals -
- Antigen Presentation - drug effects
- Antigens, Differentiation, T-Lymphocyte - biosynthesis
- Apoptosis - drug effects
- Bone Marrow Cells - drug effects
- Busulfan - analogs and derivatives
- Cell Differentiation - drug effects
- Cytokines - antagonists and inhibitors
- Dendritic Cells - cytology
- Encephalomyelitis, Autoimmune, Experimental - drug therapy
- Female - drug therapy
- Humans - drug therapy
- Immunosuppressive Agents - therapeutic use
- Injections, Intradermal - therapeutic use
- Injections, Intraperitoneal - therapeutic use
- Lymphocyte Activation - drug effects
- Lymphocytes - drug effects
- Molecular Sequence Data - drug effects
- Monocytes - cytology
- Myelin-Associated Glycoprotein - immunology
- RNA, Messenger - antagonists and inhibitors
- Rats - antagonists and inhibitors
- Rats, Inbred Strains - antagonists and inhibitors
- Research Support, Non-U.S. Gov't - antagonists and inhibitors
- T-Lymphocytes - cytology
- Find related publications in this database (Keywords)
- CNS inflammation
- chemotherapy
- animal model
- myelin
- cytokines
- apoptosis