High β-adrenoceptor density on peripheral blood mononuclear cells in progressive multiple sclerosis: a manifestation of autonomic dysfunction?

Authors

  • Y. Zoukos,

    Corresponding author
    1. Multiple Sclerosis Laboratory, University Department of Clinical Neurology, Institute of Neurology, National Hospital for Neurology and Neurosurgery and the Cardiovascular Medicine Unit, St Mary's Hospital Medical School/Imperial College of Science, Technology and Medicine, London
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  • T. Thomaides,

    1. Autonomic Unit, University Department of Clinical Neurology, Institute of Neurology, National Hospital for Neurology and Neurosurgery and the Cardiovascular Medicine Unit, St Mary's Hospital Medical School/Imperial College of Science, Technology and Medicine, London
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  • C. J. Mathias,

    1. Autonomic Unit, University Department of Clinical Neurology, Institute of Neurology, National Hospital for Neurology and Neurosurgery and the Cardiovascular Medicine Unit, St Mary's Hospital Medical School/Imperial College of Science, Technology and Medicine, London
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  • M. L. Cuzner

    1. Multiple Sclerosis Laboratory, University Department of Clinical Neurology, Institute of Neurology, National Hospital for Neurology and Neurosurgery and the Cardiovascular Medicine Unit, St Mary's Hospital Medical School/Imperial College of Science, Technology and Medicine, London
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a Institute of Neurology, Multiple Sclerosis Laboratory, 1 Wakefield Street, London, WC1N 1PJ, England

Abstract

In multiple sclerosis (MS) up-regulation of β-adrenoceptors on peripheral blood mononuclear cells (PBMCs) has been attributed to either autonomic dysfunction, inflammation or a combination of the two. We have compared secondary progressive MS patients with normal subjects (NS) and two models of autonomic dysfunction; pure autonomic failure (PAF) and multiple system atrophy (MSA, Shy-Drager syndrome). There was up-regulation of β-adrenoceptors on PBMCs in MS and PAF patients but not in MSA patients. Only in PAF patients β-adrenoceptor up-regulation was correlated with low plasma levels of noradrenaline (NA) and adrenaline (Ad). In addition to studies in the basal state, measurements also were made after the centrally acting sympatholytic agent clonidine. These were combined with haemodynamic and neurohormonal measurements. After clonidine, there was a fall in blood pressure in NS and MSA patients but not in MS and PAF patients; a rise in growth hormone (GH) in NS and PAF patients but not in MS and MSA patients; and an up-regulation in PBMCs β-adrenoceptors in NS but not in MS, MSA and PAF patients. Up-regulation of β-adrenoceptors on PBMCs in MS could be attributed to autonomic dysfunction but the disparity between MS and PAF patients when considering their plasma levels of NA and Ad argue against. Although the neurohormonal responses to clonidine and the physiological assessment of autonomic function in progressive MS patients, demonstrate central autonomic dysfunction resembling that of the MSA patients, the normal basal β-adrenoceptor densities in the latter, suggests that the up-regulation of these receptors is independent of the central autonomic dysfunction in MS.

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