Metallothionein treatment reduces proinflammatory cytokines IL-6 and TNF-α and apoptotic cell death during experimental autoimmune encephalomyelitis (EAE)

Milena Penkowa, Juan Hidalgo

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    99 Citations (Scopus)

    Abstract

    Experimental autoimmune encephalomyelitis (EAE) is an animal model for the human autoimmune disease multiple sclerosis (MS). Proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are considered important for induction and pathogenesis of EAE/MS disease, which is characterized by significant inflammation and neuroglial damage. We have recently shown that the exogenous administration of the antioxidant protein zinc-metallothionein-II (Zn-MT-II) significantly decreased the clinical symptoms, mortality, and leukocyte infiltration of the CNS during EAE. However, it is not known how EAE progression is regulated nor how cytokine production and cell death can be reduced. We here-with demonstrate that treatment with Zn-MT-II significantly decreased the CNS expression of IL-6 and TNF-α during EAE. Zn-MT-II treatment could also significantly reduce apoptotic cell death of neurons and oligodendrocytes during EAE, as judged by using TUNEL and immunoreactivity for cytochrome c and caspases 1 and 3. In contrast, the number of apoptotic lymphocytes and macrophages was less affected by Zn-MT-II treatment. The Zn-MT-II-induced decrease in proinflammatory cytokines and apoptosis during EAE could contribute to the reported diminution of clinical symptoms and mortality in EAE-immunized rats receiving Zn-MT-II treatment. Our results demonstrate that MT-II reduces the CNS expression of proinflammatory cytokines and the number of apoptotic neurons during EAE in vivo and that MT-II might be a potentially useful factor for treatment of EAE/MS. © 2001 Academic Press.
    Original languageEnglish
    Pages (from-to)1-14
    JournalExperimental Neurology
    Volume170
    DOIs
    Publication statusPublished - 1 Jan 2001

    Keywords

    • Apoptosis
    • Cytokines
    • EAE/MS
    • Immunotherapy
    • Neuroimmunology

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