INCREASED EXPRESSION OF HIGH-AFFINITY IL-2 RECEPTORS AND P-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 i ncreased number of beta-adrenoceptors and inflammatory disease has bee n further indicated by studies in rheumatoid arthritis and relapsing-r emitting multiple sclerosis patients. In a serial monthly assessment o f relapsing-remitting multiple sclerosis patients, we have demonstrate d that increased beta-adrenoceptors on PBMCs correlate with the expres sion of high affinity interleukin-2 receptors (IL-2Rs) and disease act ivity as determined by clinical and MRI findings. Magnetic resonance i maging activity was strongly correlated with IL-2R expression and it a ppears to be a sensitive marker of PBMC immunoactivation in multiple s clerosis. In vitro studies showed that beta-agonist stimulation of PBM Cs reduces the IL-2R expression and suppresses cell proliferation foll owing mitogenic stimulation. This observation may indicate a recovery role for the enhanced beta-adrenoceptor expression in multiple scleros is. However, its therapeutic importance remains to be tested by approp riate trials using either beta-agonists or agents activating the secon d messenger system, c-AMP, in lymphocytes.