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Title: Interactions between the neural, endocrine and immune systems during the course of experimental allergic encephalomyelitis (EAE)
Author: Leonard, John Patrick
Awarding Body: University of London
Current Institution: University College London (University of London)
Date of Award: 1991
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Interactions between the neural, endocrine and immune systems have been investigated during the course of experimental allergic encephalomyelitis (EAE), a cell-mediated autoimmune disease, induced by immunization with myelin basic protein (MBP) in complete Freund's adjuvant (CFA). Activation of the hypothalamic-pituitary-adrenal (HPA) axis and splenic sympathetic noradrenergic pathways was evident during the period of expected lymphoproliteration following immunization with MBP/CFA, or CFA alone, which coincided with an increase in lymphocyte B-adrenergic receptor density. During the stressful clinical stage of EAE, further activation of neural and endocrine pathways was indicated by increased splenic noradrenaline (NA) and serum corticosterone (CS) levels. Similar responses were observed when EAE was induced by the transfer of MBP-sensitized splenocytes, despite the absence of the primary immune challenge from the mycobacterial components of the adjuvant. Activation of both neural and endocrine pathways occurred prior to clinical signs. This is most likely a general response to cytokine production from stimulated cells, since comparable changes were seen in control animals following the transfer of cells sensitized to the antigenic component of the adjuvant. The importance of intact noradrenergic pathways was demonstrated by the altered clinical severity of EAE following either the destruction of central or peripheral sympathetic nerve terminals, or the administration of centrally acting sympathetic drugs. A significant inverse correlation was found between hypothalamic NA content and circulating CS, which was most evident during peak clinical signs of disease and suggests a role for central sympathetic pathways in the regulation of the HPA-axis during the course of EAE. Consistent with the changes in circulating CS, increases in pituitary pro-opiomelanocortin mRNA were found during the pre-clinical and clinical stages of the disease. However the reduced levels of hypothalamic corticotropin-releasing factor mRNA at the time of maximum clinical signs, suggests that activation of the HPA-axis results from either vasopressin release or direct activation at the level of the pituitary. The overriding immunoregulatory influence of CS was demonstrated by the rapid onset of EAE and morbidity in adrenalectomised animals. However, the compensatory increases in splenic NA and lymphocyte 15-adrenergic receptor density seen in these animals and the significant correlation between central NA and circulating CS, indicates that both central and peripheral sympathetic pathways may be activated following immune challenge and play a pivotal role in determining the outcome of disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available