Regulatory effects of cytokines and cyclosporine A on peripheral blood mononuclear cells from stable multiple sclerosis patients.

The proliferative response (PR) of peripheral blood mononuclear cells (PBMC ) to lectins such as phytohemaglutinin (PHA), anti-CD3 monoclonal antibodie s such as OKT-3 or phorbol esters such as tetradecanoyl-phorbol 13-acetate (TPA) was investigated in 18 stable multiple sclerosis (MS) patients (9 unt reated and 9 treated patients) and 10 healthy controls. PBMC from untreated MS patients showed a significantly higher PR to PHA than healthy controls. The PR of PKA, anti-CD3 or TPA stimulated PBMC from treated patients was l ower than that from untreated MS patients. Mitogen stimulated PBMC from unt reated patients shown both increased sensitivity to the stimulatory effect of IL-2 and increased resistance to the inhibitory effect of IL-10 and IFN- alpha. The addition of IL-2 increased the PR in PHA-stimulated PBMC from un treated MS patients, but not in those from treated MS patients and healthy controls. Mitogen stimulated cells from untreated patients were more resist ant to the inhibitory effect of IL-10 and IFN-alpha than PBMC from either t reated MS patients or healthy controls. Cyclosporine A (CsA) inhibited the PR and the expression of activation antigens induced by PHA in PBMC from th e three groups of subjects. This inhibitory effect of CsA have was enhanced by the addition of IFN-alpha.