Sympathetic skin responses are decreased and lymphocyte beta-adrenergic receptors are increased in progressive multiple sclerosis.
Immune abnormalities, including deficient CD8 lymphocyte-mediated suppression, have been implicated in the progression of multiple sclerosis (MS). The peripheral sympathetic branch of the autonomic nervous system innervates the lymphoid organs and affects immune function. Animals with an ablated sympathetic nervous system develop more severe experimental allergic encephalomyelitis than control animals and exhibit an increased density of beta-adrenergic receptors on their lymphocytes. Experimental allergic encephalomyelitis shares many features with MS. Accordingly, we investigated the psychogalvanic skin reflex in patients with rapidly progressive MS and found that 13 patients (57%) lacked this sympathetic-mediated response. The density of beta-adrenergic receptors on lymphocyte subsets was increased in progressive MS, most notably on the CD8 suppressor/cytotoxic subset. B lymphocytes had the greatest number of receptors with 12.1 +/- 1.8 fmol/10(6) cells in control subjects and 18.7 +/- 2.6 fmol/10(6) cells in patients with MS. CD8 lymphocytes possessed an intermediate number of receptors with 3.4 +/- 0.4 fmol/10(6) cells in control subjects and 9.1 +/- 1.6 fmol/10(6) cells in patients with MS. CD4 lymphocytes demonstrated the fewest receptors with 1.2 +/- 0.1 fmol/10(6) cells in control subjects and 1.8 +/- 0.4 fmol/10(6) cells in patients with MS. No differences in the affinity or function (cyclic adenosine monophosphate levels in response to 10(-5) M (-)isoproterenol) of the adrenergic receptor were found when patients with progressive MS and control subjects were compared. Autonomic abnormalities in progressive MS and the increased beta-adrenergic receptor density found on CD8 lymphocytes may be related.
Karaszewski
J W
JW
Department of Neurology, University of Chicago, IL 60637.
Reder
A T
AT
Maselli
R
R
Brown
M
M
Arnason
B G
BG
D000328:Adult; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000378:metabolism; D004558:Electric Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008564:Membrane Potentials; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology / Q000503:physiopathology*; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012867:Skin / Q000294:innervation*; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D013601:T-Lymphocytes / Q000378:metabolism* / Q000473:pathology
D011943:Receptors, Adrenergic, beta; C047975:cyanopindolol; D010869:Pindolol; D000242:Cyclic AMP