Concomitant Expression of IL-6 and TGF-ß Cytokines and their Receptors in Peripheral Blood of Patients with Multiple Sclerosis: The Effects of INFß Drugs.

BACKGROUND: Concomitant signals from IL-6 and TGF-ß have a central role in the Th17 cells development and differentiation, and these cells are the main promoters of demyelinating inflammation in the central nervous system (CNS) resulting in multiple sclerosis (MS). OBJECTIVES: To evaluate the simultaneous IL-6 and TGF-ß gene and their receptor protein expression in patients with Relapsing-Remitting (RR)-MS. MATERIALS AND METHODS: IL-6 and TGF-ß mRNA and their receptor expression on the surface of CD4+T cells were evaluated using real-time PCR (RT-PCR) and flow cytometry, respectively. RESULTS: The IL-6 mRNA expression in patients with RRMS was significantly higher than in the controls (p= 0.019). When patients who did not receive any other treatment were compared with the controls, the significant difference was substantial (p=0.006). The TGF-ß mRNA expression in patients was lower than in the controls (p = 0.03). However, in patients receiving IFNß, it increased compared with the other patients (p= 0.036). There was no difference in cytokine receptor expression between patients and the control group. CONCLUSION: Our data conclude an increase and decrease in mRNA expression levels of IL-6 and TGF-ß in patients with RRMS, respectively. Moreover, there were no significant differences in receptor expression of either cytokines. Based on our data the balance of TGF and IL-6 appears to have a positive impact on the disease control.

Therapeutic plasma exchange may adjust IL-6 and TGF-ß signals in relapsed MS patients peripheral blood.

OBJECTIVE: Effects of therapeutic plasma exchange (TPE) on immune cells and their cytokine production in MS, are unknown. Since interleukine-6 and tumor growth factor-ß have critical roles in MS immunopathogenesis, the impacts of TPE on the expression of these cytokines and their receptors on the surface of CD4+ T lymphocytes, were investigated. METHODS: Blood cells were obtained from 30 Relapsing-Remitting (RR) MS patients, before and after a complete TPE course. Cytokines mRNA and their receptor expression on the CD4+ T cells surface were assessed using real-time PCR and flowcytometry, respectively. RESULTS: TPE reduced symptom severity (P = .01) and the relief was higher in males than in females (P = .039). TPE also increased TGF-ß mRNA and decreased IL-6 receptor expressing cells frequency (P = .009 and P = .028, respectively). Moreover, the frequency of CD4+IL6R+ T cells was positively correlated with disease severity (P = .001). CONCLUSION: TPE impacts simultaneously on the TGF-ß mRNA and IL-6 receptor expression, and this may be a mechanism of improvement in MS relapse symptoms induced by the TPE.