ESTRIOL IN FUNCTIONAL MODULATION OF REGULATORY LYMPHOCYTES IN MULTIPLE SCLEROSIS

Abstract

We studied effects of estriol (E3), at the doses corresponding to the I and III trimesters of pregnancy,upon expression of functional markers on T-regulatory (Treg) and Th17-producing (Th17) lymphocytes, aswell as the production of relevant cytokines by the cells of patients with multiple sclerosis (MS), as comparedwith healthy donors. It was found that the levels of CD4+FoxP3+CTLA-4+ (Treg) lymphocytes in MS patientswere initially lower than those of healthy donors. Percentages of CD4+RORγt+IL-17A+ (Th17) lymphocytesdid not significantly differ from those in healthy donors, still showing a tendency for increase. Baseline levelsof IL-17 and IL-6 in cell culture supernates of MS patients were higher than in healthy donors, along withreduced contents of the anti-inflammatory IL-10 cytokine. Percentage of Tregs was increased under theinfluence of estriol, whereas Th17 proportion was diminished. These hormonal effects upon lymphocyteswere reproducible both for healthy donors, and MS patients. Moreover, estriol stimulated IL-10 productionand inhibited secretion of IL-6 and IL-17. Therefore, a sufficient release of MS symptoms observed duringpregnancy may be explained by influence of estriol, thus extending opportunities for rational use of this steroidhormone in MS treatment

Keywords

• multiple sclerosis
• estriol
• t regulatory lymphocytes
• th17 lymphocytes
• cytokines