Regulatory Effects of Cytokines and Cyclosporine A on Peripheral Blood Mononuclear Cs from Stable Multiple Sclerosis Patients

Abstract

The proliferative response (PR) of peripheral blood mononuclear cells (PBMC) to lectins such as phytohemaglutinin (PHA), anti-CD3 monoclonal antibodies such as OKT-3 or phorbol esters such as tetradecanoyl-phorbol 13-acetate (TPA) was investigated in 18 stable multiple sclerosis (MS) patients (9 untreated 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 PHA, anti-CD3 or TPA stimulated PBMC from treated patients was lower than that from untreated MS patients. Mitogen stimulated PBMC from untreated 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 untreated MS patients, but not in those from treated MS patients and healthy controls. Mitogen stimulated cells from untreated patients were more resistant to the inhibitory effect of IL-10 and IFN-alpha than PBMC from either treated MS patients or healthy controls. Cyclosporine A (CsA) inhibited the PR and the expression of activation antigens induced by PHA in PBMC from the three groups of subjects. This inhibitory effect of CsA have was enhanced by the addition of IFN-alpha.

The Role of Interferon-α in Neurodegenerative Diseases: A Systematic Review

“…IFN-␣ was shown to be effective in decreasing the rate of relapse and stabilizing patients with MS. Those who were treated with a longer duration and a higher dosage also had a greater reduction in Extended Disability Status Scale (EDSS). In addition, Guillen et al found that IFN-␣ was able to enhance the effect of cyclosporin in treating MS [83]. Hence, IFN-␣ was shown to be beneficial in MS.…”

Evaluation of apoptosis-related genes; Fas (CD94), FasL (CD178) and TRAIL polymorphisms in Iranian multiple sclerosis patients

“…Inadequate activation of T lymphocytes usually leads to a state of vulnerability to programmed cell death [23]. Abnormal immune responses with dysregulation of different components of the immune system (mainly abnormal activation of T cells and accessory cells) have fundamental mechanisms in MS pathogenesis induction [24]. Polymorphisms of the Fas_ -670A/G lead to disruption in the function of stimulatory protein 1 (Sp1) and the signal transducer and activator of transcription 1 (STAT1) protein binding element, respectively, diminishing the promoter activity and decreasing Fas expression [7].…”