Author:
Gold Stefan M,Chalifoux Sara,Giesser Barbara S,Voskuhl Rhonda R
Abstract
Abstract
Background
Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a pronounced neurodegenerative component. It has been suggested that novel treatment options are needed that target both aspects of the disease. Evidence from basic and clinical studies suggests that testosterone has an immunomodulatory as well as a potential neuroprotective effect that could be beneficial in MS.
Methods
Ten male MS patients were treated with 10 g of gel containing 100 mg of testosterone in a cross-over design (6 month observation period followed by 12 months of treatment). Blood samples were obtained at three-month intervals during the observation and the treatment period. Isolated blood peripheral mononuclear cells (PBMCs) were used to examine lymphocyte subpopulation composition by flow cytometry and ex vivo protein production of cytokines (IL-2, IFNγ, TNFα, IL-17, IL-10, IL-12p40, TGFβ1) and growth factors (brain-derived neurotrophic factor BDNF, platelet-derived growth factor PDGF-BB, nerve growth factor NGF, and ciliary neurotrophic factor CNTF). Delayed type hypersensitivity (DTH) skin recall tests were obtained before and during treatment as an in vivo functional immune measure.
Results
Testosterone treatment significantly reduced DTH recall responses and induced a shift in peripheral lymphocyte composition by decreasing CD4+ T cell percentage and increasing NK cells. In addition, PBMC production of IL-2 was significantly decreased while TGFβ1 production was increased. Furthermore, PBMCs obtained during the treatment period produced significantly more BDNF and PDGF-BB.
Conclusion
These results are consistent with an immunomodulatory effect of testosterone treatment in MS. In addition, increased production of BDNF and PDGF-BB suggests a potential neuroprotective effect.
Trial Registration
NCT00405353 http://www.clinicaltrials.gov
Publisher
Springer Science and Business Media LLC
Subject
Cellular and Molecular Neuroscience,Neurology,Immunology,General Neuroscience
Reference41 articles.
1. McFarland HF, Martin R: Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol. 2007, 8: 913-9. 10.1038/ni1507.
2. Hemmer B, Hartung HP: Toward the development of rational therapies in multiple sclerosis: what is on the horizon?. Ann Neurol. 2007, 62: 314-26. 10.1002/ana.21289.
3. Bebo BF, Zelinka-Vincent E, Adamus G, Amundson D, Vandenbark AA, Offner H: Gonadal hormones influence the immune response to PLP 139–151 and the clinical course of relapsing experimental autoimmune encephalomyelitis. J Neuroimmunol. 1998, 84: 122-130. 10.1016/S0165-5728(97)00214-2.
4. Smith ME, Eller NL, McFarland HF, Racke MK, Raine CS: Age dependence of clinical and pathological manifestations of autoimmune demyelination. Implications for multiple sclerosis. Am J Pathol. 1999, 155: 1147-1161.
5. Ahmed SA, Penhale WJ: The influence of testosterone on the development of autoimmune thyroiditis in thymectomized and irradiated rats. Clin Exp Immunol. 1982, 48: 367-374.
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