Testosterone therapy ameliorates experimental autoimmune encephalomyelitis and induces a T helper 2 bias in the autoantigen-specific T lymphocyte response.
Female SJL mice are more susceptible than male mice to experimental autoimmune encephalomyelitis (EAE) induced by myelin basic protein (MBP)-specific T lymphocytes. In the present study, we examined mechanisms involved in this gender-related difference in disease susceptibility. MBP-specific T lymphocytes derived from spleens of males during the effector phase of adoptive EAE produced significantly higher levels of IL-10, an anti-inflammatory cytokine in EAE. A protective effect of testosterone was then shown. Females implanted with dihydrotestosterone pellets demonstrated a significantly less severe course of EAE as compared with females implanted with placebo pellets. Finally, MBP-specific T lymphocytes derived from dihydrotestosterone-implanted females produced significantly higher levels of IL-10 than those from placebo. Together these data indicate that testosterone exerts a protective effect in EAE that is mediated at least in part by enhanced production of IL-10 by autoantigen-specific T lymphocytes.
Dalal
M
M
UCLA Multiple Sclerosis Center, UCLA Department of Neurology, Los Angeles, CA 90095, USA.
Kim
S
S
Voskuhl
R R
RR
D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology*; D008297:Male; D051379:Mice; D004676:Myelin Basic Protein / Q000276:immunology*; D012737:Sex Factors; D013739:Testosterone / Q000627:therapeutic use*; D018418:Th2 Cells / Q000276:immunology*
D001324:Autoantigens; D004676:Myelin Basic Protein; D016753:Interleukin-10; D013739:Testosterone