Interferon (IFN)-Y-induced intracellular calcium increase in T lymphocytes from patfents with multiple sclerosis precedes clinical exacerbation and detection of active lesions on MRI

Interferon (IFN)-γ exerts a multiplicity of actions potentially relevant for the pathogenesis of multiple sclerosis, including the expression of a transplasmalemma calcium (Ca 2+) influx leading to an intracellular Ca 2+ ( [Ca 2+] i) increase able to lower T lymphocytes threshold of excitability. We assessed the temporal relationship between disease activity, detected by MRI, and the IFN-γ activated Ca 2+ influx, measured by a fluorimetric analysis on peripheral blood lymphocytes from patient with relapsingremitting MS every 15 days for 1 year. The influx was detected a mean of 10.4 (range 7-17) Cimesei patient. Fluctations of the influx correlated with clinical events (p=0.04) and monthly enhanced brain MRI (p=0.05). Peak [Ca 2+] 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 Ca 2+ mediated phenomena.