In vitro correction of the interleukin-2 and interferon-gamma defect in multiple sclerosis

The effect of phytohaemagglutinin (PHA) and/or phorbol myristic acetate (PMA) on human interferon-gamma (HuIFN-gamma) and interleukin 2 (IL-2) production was measured in peripheral blood leucocytes (PBL) from multiple sclerosis (MS) patients. Seven out of 12 MS patients studied had PBLs which were unable to produce any detectable HuIFN-gamma after stimulation with PHA. The PBL cultures of the same seven patients were also defective for IL-2 production after PHA stimulation. Addition of PMA before and during PHA stimulation resulted in restored IL-2 and HuIFN-gamma production in all otherwise non-responsive cultures. In MS cultures responsive to PHA alone, the addition of PMA resulted in a 10-fold increase of HuIFN-gamma and IL-2 production. Analysis of interleukin 1 (IL-1) production by peripheral blood monocytes (PBM) isolated from the same cultures, revealed that both spontaneous and PMA-induced IL-1 yield was the same for all cultures tested, regardless whether they produced IL-2 and HuIFN-gamma after PHA stimulation or not.