Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone.
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, IFNgamma, TNFalpha, IL-17, IL-10, IL-12p40, TGFbeta1) 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 TGFbeta1 production was increased. Furthermore, PBMCs obtained during the treatment period produced significantly more BDNF and PDGF-BB.


CONCLUSIONS
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.


BACKGROUND
NCT00405353 http://www.clinicaltrials.gov.
Gold
Stefan M
SM
Department of Neurology, Neuroscience Research Building 1, 635 Charles E, Young Drive South, University of California Los Angeles, CA 90095, USA. sgold@mednet.ucla.edu
Chalifoux
Sara
S
Giesser
Barbara S
BS
Voskuhl
Rhonda R
RR
D000328:Adult; D000818:Animals; D002478:Cells, Cultured; D018592:Cross-Over Studies; D016207:Cytokines / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007107:Immune System / Q000187:drug effects / Q000276:immunology; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D013739:Testosterone / Q000494:pharmacology / Q000627:therapeutic use
D016207:Cytokines; D007155:Immunologic Factors; D036341:Intercellular Signaling Peptides and Proteins; D018698:Glutamic Acid; D013739:Testosterone