Cytosine arabinoside induced changes in natural killer and antibody dependent cellular cytotoxicity functions in multiple sclerosis patients.

Abstract

Five multiple sclerosis patients were treated weekly with cytosine arabinoside (araC) on an escalating dose schedule. The dose was initiated at 50 mg/M2 and then increased once each week by 50 mg/M2 (unless toxicity caused delay). Dosage decisions were based on whether or not the antibody-dependent cellular-cytotoxicity (ADCC) or natural killer (NK) cytotoxicity levels had been reduced to a level more than 2 standard deviations below the control range. Cytosine arabinoside treatment was discontinued in 2 of 5 subjects at doses of 500 mg/M2 due to toxicity. The 3 remaining patients demonstrated sustained reductions in the percentage of FcR+ cells in their peripheral blood. The maximum percentage reductions from the baseline values ranged from 50% to 76%. Concomitant reductions in the NK activity at the same doses ranged from 65% to 83%. ADCC activity in all 3 patients, however, was relatively resistant to suppression. The nadirs for the ADCC activity were only 16% to 44% below the baseline minimum. AraC was shown to reduce the proportion of FcR+ cells and NK cytotoxic activity in preference to ADCC activity.