Disease progression in chronic relapsing experimental allergic encephalomyelitis is associated with reduced inflammation-driven production of corticosterone

A. Stefferl, M. K. Storch, Christopher Linington, C. Stadelmann, H. Lassmann, T. Pohl, F. Holsboer, F. J. H. Tilders, J. M. H. M. Reul

    Research output: Contribution to journalArticle

    44 Citations (Scopus)

    Abstract

    In this study, we demonstrate that disruption of neuroendocrine signaling is a major factor driving disease progression in myelin oligodendrocyte glycoprotein-induced chronic relapsing experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Although the initial episode of chronic relapsing experimental autoimmune encephalomyelitis is associated with a robust hypothalamic-pituitary-adrenocortical axis response, we show that subsequent disease progression is associated with a selective desensitization of hypothalamic-pituitary-adrenocortical responsiveness to inflammatory mediators. Inflammatory activity in the central nervous system during relapse is therefore unable to produce an endogenous immunosuppressive corticosterone response, and disease progresses into an ultimately lethal phase. However, disease progression is inhibited if the circulating corticosterone level is maintained at levels seen during the initial phase of disease. The effect of hypothalamic-pituitary-adrenocortical axis desensitization on the clinical course of experimental autoimmune encephalomyelitis is aggravated by a marked reduction in proinflammatory cytokine synthesis in the central nervous system in the later stages of disease, reflecting an increasing involvement of antibody, rather than T cell-dependent effector mechanisms, in disease pathogenesis, with time. Thus, our data indicate that distinct immune-endocrine effects play a decisive role in determining disease progression in multiple sclerosis, a concept supported by reports that a subpopulation of multiple sclerosis patients shows evidence of hypothalamic-pituitary-adrenocortical axis desensitization.

    Original languageEnglish
    Pages (from-to)3616-3624
    Number of pages8
    JournalEndocrinology
    Volume142
    DOIs
    Publication statusPublished - 2001

    Keywords

    • MYELIN OLIGODENDROCYTE GLYCOPROTEIN
    • EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
    • CORTICOTROPIN-RELEASING FACTOR
    • PITUITARY-ADRENAL AXIS
    • MULTIPLE-SCLEROSIS
    • MEDIATED DEMYELINATION
    • NERVOUS-SYSTEM
    • T-CELLS
    • RAT
    • RECEPTOR

    Cite this

    Disease progression in chronic relapsing experimental allergic encephalomyelitis is associated with reduced inflammation-driven production of corticosterone. / Stefferl, A.; Storch, M. K.; Linington, Christopher; Stadelmann, C.; Lassmann, H.; Pohl, T.; Holsboer, F.; Tilders, F. J. H.; Reul, J. M. H. M.

    In: Endocrinology, Vol. 142, 2001, p. 3616-3624.

    Research output: Contribution to journalArticle

    Stefferl, A, Storch, MK, Linington, C, Stadelmann, C, Lassmann, H, Pohl, T, Holsboer, F, Tilders, FJH & Reul, JMHM 2001, 'Disease progression in chronic relapsing experimental allergic encephalomyelitis is associated with reduced inflammation-driven production of corticosterone', Endocrinology, vol. 142, pp. 3616-3624. https://doi.org/10.1210/en.142.8.3616
    Stefferl, A. ; Storch, M. K. ; Linington, Christopher ; Stadelmann, C. ; Lassmann, H. ; Pohl, T. ; Holsboer, F. ; Tilders, F. J. H. ; Reul, J. M. H. M. / Disease progression in chronic relapsing experimental allergic encephalomyelitis is associated with reduced inflammation-driven production of corticosterone. In: Endocrinology. 2001 ; Vol. 142. pp. 3616-3624.
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    abstract = "In this study, we demonstrate that disruption of neuroendocrine signaling is a major factor driving disease progression in myelin oligodendrocyte glycoprotein-induced chronic relapsing experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Although the initial episode of chronic relapsing experimental autoimmune encephalomyelitis is associated with a robust hypothalamic-pituitary-adrenocortical axis response, we show that subsequent disease progression is associated with a selective desensitization of hypothalamic-pituitary-adrenocortical responsiveness to inflammatory mediators. Inflammatory activity in the central nervous system during relapse is therefore unable to produce an endogenous immunosuppressive corticosterone response, and disease progresses into an ultimately lethal phase. However, disease progression is inhibited if the circulating corticosterone level is maintained at levels seen during the initial phase of disease. The effect of hypothalamic-pituitary-adrenocortical axis desensitization on the clinical course of experimental autoimmune encephalomyelitis is aggravated by a marked reduction in proinflammatory cytokine synthesis in the central nervous system in the later stages of disease, reflecting an increasing involvement of antibody, rather than T cell-dependent effector mechanisms, in disease pathogenesis, with time. Thus, our data indicate that distinct immune-endocrine effects play a decisive role in determining disease progression in multiple sclerosis, a concept supported by reports that a subpopulation of multiple sclerosis patients shows evidence of hypothalamic-pituitary-adrenocortical axis desensitization.",
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    AU - Stefferl, A.

    AU - Storch, M. K.

    AU - Linington, Christopher

    AU - Stadelmann, C.

    AU - Lassmann, H.

    AU - Pohl, T.

    AU - Holsboer, F.

    AU - Tilders, F. J. H.

    AU - Reul, J. M. H. M.

    PY - 2001

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    N2 - In this study, we demonstrate that disruption of neuroendocrine signaling is a major factor driving disease progression in myelin oligodendrocyte glycoprotein-induced chronic relapsing experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Although the initial episode of chronic relapsing experimental autoimmune encephalomyelitis is associated with a robust hypothalamic-pituitary-adrenocortical axis response, we show that subsequent disease progression is associated with a selective desensitization of hypothalamic-pituitary-adrenocortical responsiveness to inflammatory mediators. Inflammatory activity in the central nervous system during relapse is therefore unable to produce an endogenous immunosuppressive corticosterone response, and disease progresses into an ultimately lethal phase. However, disease progression is inhibited if the circulating corticosterone level is maintained at levels seen during the initial phase of disease. The effect of hypothalamic-pituitary-adrenocortical axis desensitization on the clinical course of experimental autoimmune encephalomyelitis is aggravated by a marked reduction in proinflammatory cytokine synthesis in the central nervous system in the later stages of disease, reflecting an increasing involvement of antibody, rather than T cell-dependent effector mechanisms, in disease pathogenesis, with time. Thus, our data indicate that distinct immune-endocrine effects play a decisive role in determining disease progression in multiple sclerosis, a concept supported by reports that a subpopulation of multiple sclerosis patients shows evidence of hypothalamic-pituitary-adrenocortical axis desensitization.

    AB - In this study, we demonstrate that disruption of neuroendocrine signaling is a major factor driving disease progression in myelin oligodendrocyte glycoprotein-induced chronic relapsing experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis. Although the initial episode of chronic relapsing experimental autoimmune encephalomyelitis is associated with a robust hypothalamic-pituitary-adrenocortical axis response, we show that subsequent disease progression is associated with a selective desensitization of hypothalamic-pituitary-adrenocortical responsiveness to inflammatory mediators. Inflammatory activity in the central nervous system during relapse is therefore unable to produce an endogenous immunosuppressive corticosterone response, and disease progresses into an ultimately lethal phase. However, disease progression is inhibited if the circulating corticosterone level is maintained at levels seen during the initial phase of disease. The effect of hypothalamic-pituitary-adrenocortical axis desensitization on the clinical course of experimental autoimmune encephalomyelitis is aggravated by a marked reduction in proinflammatory cytokine synthesis in the central nervous system in the later stages of disease, reflecting an increasing involvement of antibody, rather than T cell-dependent effector mechanisms, in disease pathogenesis, with time. Thus, our data indicate that distinct immune-endocrine effects play a decisive role in determining disease progression in multiple sclerosis, a concept supported by reports that a subpopulation of multiple sclerosis patients shows evidence of hypothalamic-pituitary-adrenocortical axis desensitization.

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    KW - PITUITARY-ADRENAL AXIS

    KW - MULTIPLE-SCLEROSIS

    KW - MEDIATED DEMYELINATION

    KW - NERVOUS-SYSTEM

    KW - T-CELLS

    KW - RAT

    KW - RECEPTOR

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    ER -