Immune modulation and increased neurotrophic factor production in multiple sclerosis patients treated with testosterone

Stefan M Gold,Barbara S Giesser,Sara Chalifoux,Rhonda R Voskuhl

doi:10.1186/1742-2094-5-32

Abstract

BackgroundMultiple 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.MethodsTen 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.ResultsTestosterone 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.ConclusionThese 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 RegistrationNCT00405353

Highlights

Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a pronounced neurodegenerative component
These results are consistent with an immunomodulatory effect of testosterone treatment in Multiple sclerosis (MS)
Delayed type hypersensitivity (DTH) recall responses were significantly decreased during treatment compared to pre

Summary

Introduction

Multiple sclerosis is a chronic inflammatory disease of the central nervous system with a pronounced neurodegenerative component. 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. It is currently thought that potential new treatments should ideally have anti-inflammatory as well as neuroprotective properties [2]. Testosterone treatment ameliorates EAE [9]. These protective effects are thought to be mediated by testosterone's immunomodulatory properties such as decreasing the production of pro-inflammatory cytokines TNFα and IL-1β by macrophages [10] and monocytes [11] as well as increasing production of the anti-inflammatory cytokine IL-10 by T cells [12]

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