ABSTRACT
Multiple sclerosis (MS) is a neurological disorder that causes disability and paralysis, especially among young adults. Although interactions of several factors, such as viral infections, autoimmunity, genetic and environmental factors, performance a role in the beginning and progression of the disease, the exact cause of MS is unknown to date. Different immune cells such as Th1 and Th17 play an impressive role in the immunopathogenesis of MS, while, regulatory cells such as Th2 and Treg diminish the severity of the illness. Sex hormones have a vital role in many autoimmune disorders, including multiple sclerosis. Testosterone, estrogen and progesterone have various roles in the progress of MS, which higher prevalence of disease in women and more severe in men reveals the importance of sex hormones' role in this disease. Vitamin D after chemical changes in the body, as an active hormone called calcitriol, plays an important role in regulating immune responses and improves MS by modulating the immune system. The optimum level of calcium in the body with vitamin D modulates immune responses and calcium as an essential ion in the body plays a key role in the treatment of autoimmune diseases. The interaction between vitamin D and sex hormones has protective and therapeutic effects against MS and functional synergy between estrogen and calcitriol occurs in disease recovery. Moreover, vitamin D and calcium interact with each other to regulate the immune system and shift them to anti-inflammatory responses.
ABSTRACT
Multiple sclerosis (MS) is a complex inflammatory and demyelinating disease of the central nervous system (CNS) frequently starts in young adulthood. Demyelination, inflammatory and axonal damage in the CNS is the pathological hallmark of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. 1, 25-dihydroxyvitamin D3 (Vitamin D3) is involved in calcium regulation, phosphorus homeostasis, and bone mineralization. In addition, vitamin D3 has potential inhibitory effects on immune cells in various inflammatory and autoimmunity disease. C57BL/6 female mice were divided into prevention groups (low, middle and high doses) and treatment groups (middle and high doses). Prevention groups received vitamin D3 2 weeks before EAE induction, and treatment groups were treated with vitamin D3 simultaneous with EAE induction. Vitamin D3 inhibits the development of EAE in a dose-dependent manner. Histological studies revealed reduced demyelination and limited infiltration into CNS, moreover vitamin D3 increased the production of IL-4, IL-10, and TGF-ß, while a significant reduction in the production of IFN-γ, IL-6, TNF-α, and IL-17 was observed. Flow cytometry results for CD4+ T cell subsets in compliance with ELISA cytokine assay results showed a significant decrease in the percentage of Th1 and Th17, but also a significant increase in the percentage of Th2 and Treg for middle and high dose vitamin D3 treated mice. Real-time PCR results indicated that middle and high dose vitamin D3 treatment reduced T-bet and ROR-γt expression, but enhanced GATA3 and Foxp3 expression. Real-Time PCR results in CNS for T cell subsets related cytokines and transcription factors supported the results of flow cytometry and ELISA. This study indicated that middle and high doses of vitamin D3 deviate the balance between Th1/Th2 and Th17/Treg to Th2 and Treg. Moreover, vitamin D3 could reduce the incidence and severity of EAE clinical disease.
