A synthetic androstene derivative and a natural androstene metabolite inhibit relapsing–remitting EAE
| Autor: | Dominick L. Auci, Agata Matejuk, Halina Offner, Arthur A. Vandenbark, Heather Drought, Elizabeth E Morgan, Christopher L. Reading, Alex Zamora |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male medicine.medical_specialty Encephalomyelitis Autoimmune Experimental Proteolipid protein 1 T cell Encephalomyelitis Immunology Central nervous system Mice Inbred Strains Mice Multiple Sclerosis Relapsing-Remitting Sex Factors Fluasterone immune system diseases Internal medicine medicine Demyelinating disease Animals Immunology and Allergy Lymphocytes RNA Messenger Myelin Proteolipid Protein Androstenols Tumor Necrosis Factor-alpha business.industry Multiple sclerosis Dehydroepiandrosterone medicine.disease medicine.anatomical_structure Endocrinology Neurology Immunoglobulin G Androstenes Female Neurology (clinical) business Cell Division Immunosuppressive Agents Hormone |
| Zdroj: | Journal of Neuroimmunology. 130:128-139 |
| ISSN: | 0165-5728 |
| DOI: | 10.1016/s0165-5728(02)00214-x |
| Popis: | Experimental allergic encephalomyelitis (EAE), a Th1 polarized demyelinating disease of the central nervous system (CNS), shares many pathological and clinical similarities with multiple sclerosis (MS), and thus represents an attractive animal model for this disease. The goal of this study was to evaluate the suppressive effects of fluasterone (HE2500), a synthetic androstene derivative, and androstenetriol (HE2200), a natural androstene hormone on EAE. SJL mice were immunized with proteolipid protein (PLP) 139-151 peptide/CFA to induce EAE. Starting on day -7, animals were given daily injections (s.c.) of derivatives (3.0 mg) in vehicle, or vehicle alone for 33 days. Both HE2500 and HE2200 significantly delayed the onset, reduced the peak clinical score and cumulative disease index of EAE, and prevented or significantly attenuated relapses. Lower doses or other routes of administration were less effective. Moreover, T cells from treated mice had significantly reduced PLP 139-151-specific T cell proliferation responses and reduced numbers of TNF-alpha- and IFN-gamma-producing cells in the CNS. Daily treatment of B10.PL mice with HE2500, starting on day 0, completely prevented the development of disease in these animals. Finally, SJL mice treated with HE2500 at EAE onset showed significantly reduced mean clinical scores. Thus, these compounds, which have been reported to have a few androgenic or estrogenic side effects, appear to have a potent inhibitory activity in EAE. These observations suggest that HE2500 and/or HE2200 limit the production of autoimmune Th1 associated cytokines, and ultimately may be beneficial for patients with MS or other autoimmune diseases. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect