Administration of dehydroepiandrosterone suppresses experimental allergic encephalomyelitis in SJL/J mice.
Experimental allergic encephalomyelitis (EAE) is a Th1-mediated inflammatory demyelinating disease in the CNS, an animal model of multiple sclerosis. We have examined the effect of dehydroepiandrosterone (DHEA) on the development of EAE in mice. The addition of DHEA to cultures of myelin basic protein-primed splenocytes resulted in a significant decrease in T cell proliferation and secretion of (pro)inflammatory cytokines (IFN-gamma, IL-12 p40, and TNF-alpha) and NO in response to myelin basic protein. These effects were associated with a decrease in activation and translocation of NF-kappaB. In vivo administration of DHEA significantly reduced the severity and incidence of acute EAE, along with a decrease in demyelination/inflammation and expressions of (pro)inflammatory cytokines in the CNS. These studies suggest that DHEA has potent anti-inflammatory properties, which at least are in part mediated by its inhibition of NF-kappaB activation.
Du
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Department of Neurology, Multiple Sclerosis Research Center, Vanderbilt University Medical Center, Nashville, TN 37212, USA. caigan.du@mcmail.vanderbilt.edu
Khalil
M W
MW
Sriram
S
S
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D003687:Dehydroepiandrosterone / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D005260:Female; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D004676:Myelin Basic Protein / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D013116:Spinal Cord / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000893:Anti-Inflammatory Agents; D004676:Myelin Basic Protein; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D009569:Nitric Oxide; D003687:Dehydroepiandrosterone; D007371:Interferon-gamma