HIGH BETA-ADRENOCEPTOR DENSITY ON PERIPHERAL-BLOOD MONONUCLEAR-CELLS IN PROGRESSIVE MULTIPLE-SCLEROSIS - A MANIFESTATION OF AUTONOMIC DYSFUNCTION

In multiple sclerosis (MS) up-regulation of beta-adrenoceptors on peri pheral blood mononuclear cells (PBMCs) has been attributed to either a utonomic dysfunction, inflammation or a combination of the two. We hav e 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 beta-adrenoceptors on PBMCs in MS and PAF patients but n ot in MSA patients. Only in PAF patients beta-adrenoceptor up-regulati on was correlated with low plasma levels of noradrenaline (NA) and adr enaline (Ad). In addition to studies in the basal state, measurements also were made after the centrally acting sympatholytic agent clonidin e. These were combined with haemodynamic and neurohormonal measurement s. After clonidine, there was a fall in blood pressure in NS and MSA p atients 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-regu lation in PBMCs beta-adrenoceptors in NS but not in MS, MSA and PAF pa tients. Up-regulation of beta-adrenoceptors on PBMCs in MS could be at tributed to autonomic dysfunction but the disparity between MS and PAF patients when considering their plasma levels of NA and Ad argue agai nst. Although the neurohormonal responses to clonidine and the physiol ogical assessment of autonomic function in progressive MS patients, de monstrate central autonomic dysfunction resembling that of the MSA pat ients, the normal basal beta-adrenoceptor densities in the latter, sug gests that the up-regulation of these receptors is independent of the central autonomic dysfunction in MS.