INTERFERON CALCIUM PATIENTS CLINICAL ACTIVE LESIONS ON MRI (IFN)-y-INDUCED INTRACELLULAR T LYMPHOCYTES FROM PATIENTS WITH MULTIPLE SCLEROSIS PRECEDES CLINICAL EXACERBATION AND DETECTION OF ACTIVE LESIONS ON MRI

Interferon (IFN)-gamma exerts a multiplicity of actions potentially relevant for the pathogenesis of multiple sclerosis, including the expression of a transplasmalemma calcium (Ca2+) influx leading to an intracellular Ca2+ ([Ca2+]i) increase able to lower T lymphocytes threshold of excitability. We assessed the temporal relationship between disease activity, detected by MRI, and the IFN-y activated Ca2+ influx, measured by a fluorimetric analysis on peripheral blood lymphocytes from patient with relapsing- remitting MS every 15 days for I year. The influx was detected a mean of 10.4 (range 7-17) times per patient. Fluctations of the influx correlated with clinical events (p=0.04) and monthly enhanced brain MRI (p=0.05). Peak [Ca2+]i increases preceded clinical attacks or maximal detection of brain MRI enhancing lesions by a mean of 30.8 and 34.2 days respectively. The presence of the influx correlated (p=0.03) with patients' exacerbation rate. We conclude that intracellular events leading to T lymphocyte activation in multiple sclerosis occur in the peripheral blood before CNS specific events become evident and are, in part, sustained by cytokine induced Ca2+ mediated phenomena.