INTERFERON-PRODUCTION BY CULTURED PERIPHERAL LEUKOCYTES OF MS PATIENTS

Abstract

Peripheral blood leukocytes from multiple sclerosis (MS) patients and from normal individuals were tested for their interferon (IFN) producing capacity after stimulation in vitro with various lectins and viruses. The lectins, Con A [concanavalin A], PHA [phytohemagglutinin] and PWM [pokeweed mitogen], induced IFN-.gamma.. In a kinetic study, the response to Con A revealed itself as an all or none event. The number of responding cultures increased with increasing mitogen dose, but the IFN yield in responding cultures did not differ significantly between dose levels. Thus, any patient or donor could easily be rated as a responder or nonresponder. About 1/2 of the MS patients were nonresponders if Con A or PHA were used as stimuli. Ninety percent of the normal donors on the other hand were responders. With PWM as a stimulus 100% of the MS patients and normal donor groups were responders. Also, with PWM very small doses were sufficient to obtain a 100% response rate among tested cultures, and IFN production persisted for 5 days. With Con A or PHA it was arrested after 2-3 days. The MS associated lesion is apparently not the absence of functional impairment of all IFN-.gamma. producing cells, but in only a fraction of them or in an accessory cell population required for the response to Con A and PHA but not to PWM. Newcastle disease virus (NDV) and vesicular stomatitis virus (VSV) both induced IFN-.alpha.. With NDV as the inducer response rates were 100% and yields were high irrespective of whether the cells were derived from patients or control donors. In contrast, with VSV as the inducer lower response rates were found in cultures from MS patients than in those from controls.