Increased expression of high affinity IL-2 receptors and beta-adrenoceptors on peripheral blood mononuclear cells is associated with clinical and MRI activity in multiple sclerosis.
Enhanced expression of beta-adrenoceptor densities on peripheral blood mononuclear cells (PBMCs) in progressive multiple sclerosis patients has been observed in a number of independent studies. A link between increased number of beta-adrenoceptors and inflammatory disease has been further indicated by studies in rheumatoid arthritis and relapsing-remitting multiple sclerosis patients. In a serial monthly assessment of relapsing-remitting multiple sclerosis patients, we have demonstrated that increased beta-adrenoceptors on PBMCs correlate with the expression of high affinity interleukin-2 receptors (IL-2Rs) and disease activity as determined by clinical and MRI findings. Magnetic resonance imaging activity was strongly correlated with IL-2R expression and it appears to be a sensitive marker of PBMC immunoactivation in multiple sclerosis. In vitro studies showed that beta-agonist stimulation of PBMCs reduces the IL-2R expression and suppresses cell proliferation following mitogenic stimulation. This observation may indicate a recovery role for the enhanced beta-adrenoceptor expression in multiple sclerosis. However, its therapeutic importance remains to be tested by appropriate trials using either beta-agonists or agents activating the second messenger system, c-AMP, in lymphocytes.
Zoukos
Y
Y
Multiple Sclerosis Laboratory, National Hospital for Neurology and Neurosurgery, London, UK.
Kidd
D
D
Woodroofe
M N
MN
Kendall
B E
BE
Thompson
A J
AJ
Cuzner
M L
ML
D000328:Adult; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology; D009103:Multiple Sclerosis / Q000378:metabolism* / Q000473:pathology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism*
D008934:Mitogens; D011943:Receptors, Adrenergic, beta; D015375:Receptors, Interleukin-2