myelin-basic-protein and Vitamin-D-Deficiency

Topics: B-Lymphocytes; Canada; Environment; Epstein-Barr Virus Infections; Female; Genetic Predisposition to Disease; Geography, Medical; Herpesvirus 4, Human; HLA-DRB1 Chains; Humans; Male; Meta-Analysis as Topic; Multiple Sclerosis; Myelin Basic Protein; Myelin Sheath; Myeloid Cells; Risk Factors; T-Lymphocytes; Vitamin D Deficiency

Multiple sclerosis incidence is clearly inversely related to sun exposure. This observation led to the idea that vitamin D might be responsible for this relationship. Providing super-physiologic doses of the hormonal form of vitamin D, 1α,25-dihydroxyvitamin D₃, suppresses an animal model of multiple sclerosis, i.e. experimental autoimmune encephalomyelitis (EAE) but causes unwanted hypercalcemia. Further, dietary calcium is needed for this activity of 1α,25-dihydroxyvitamin D₃. B10PL mice were maintained on a vitamin D-deficient diet for two generations to produce frank vitamin D deficiency. These animals showed delayed onset and reduced severity of EAE compared to control animals on the same diet and given vitamin D₃ or provided a vitamin D-containing chow diet. Thus, vitamin D deficiency interferes with the development of this autoimmune disease rather than increasing susceptibility.

Topics: Animals; Calcitriol; Calcium; Calcium, Dietary; Encephalomyelitis, Autoimmune, Experimental; Female; Immunization; Male; Mice; Myelin Basic Protein; Pregnancy; Time Factors; Vitamin D; Vitamin D Deficiency

Topics: Axons; Causality; HLA Antigens; Humans; Interferon-gamma; Interleukin-1; Matrix Metalloproteinases; Multiple Sclerosis; Myelin Basic Protein; T-Lymphocytes; Tumor Necrosis Factor-alpha; Vitamin D Deficiency

The disease mechanism of multiple sclerosis (MS) involves inflammation, demyelination and neurodegeneration. The relation between these components is not completely understood, but recent experiences with aggressive anti-inflammatory treatment suggest that inflammation drives neuronal damage in patients with relapsing remitting MS. Although infiltration of lymphocytes into the brain parenchyma was recognized as a key event in the pathogenesis of MS more than 120 years ago, important aspects of the mechanisms triggering and sustaining this immune response remain unknown. Furthermore, studies of MS lesions and evidence from therapeutic trials suggest that the disease mechanism may vary both throughout the disease course and between patients. The understanding of MS as an autoimmune disease targeting myelin proteins is shaped by the animal model experimental autoimmune encephalomyelitis (EAE), but translation from EAE to MS has proven to be difficult. Although both the EAE model and the prominent association to HLA class II molecules suggest a key role for CD4+ T helper cells, it is not known if or how their tolerance to myelin proteins or other putative autoantigens are broken in MS. This paper reviews some important concepts and controversies in the understanding of the immunological basis for MS and its treatment.

Topics: Animals; Antigen Presentation; B-Lymphocytes; CD4-Positive T-Lymphocytes; Encephalomyelitis, Autoimmune, Experimental; Herpesvirus 4, Human; HLA Antigens; Humans; Immune Tolerance; Immunity, Cellular; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Myelin Basic Protein; Myelin Sheath; Vitamin D Deficiency

Experimental autoimmune encephalomyelitis (EAE) is an autoimmune disease believed to be a model for the human disease multiple sclerosis (MS). Induced by immunizing B10.PL mice with myelin basic protein (MBP), EAE was completely prevented by the administration of 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. 1,25-(OH)2D3 could also prevent the progression of EAE when administered at the appearance of the first disability symptoms. Withdrawal of 1,25-(OH)2D3 resulted in a resumption of the progression of EAE. Thus, the block by 1,25-(OH)2D3 is reversible. A deficiency of vitamin D resulted in an increased susceptibility to EAE. Thus, 1,25-(OH)2D3 or its analogs are potentially important for treatment of MS.

Topics: Animals; Calcitriol; Disease Progression; Encephalomyelitis, Autoimmune, Experimental; Female; Guinea Pigs; Humans; Male; Mice; Mice, Inbred Strains; Multiple Sclerosis; Mycobacterium tuberculosis; Myelin Basic Protein; Spinal Cord; Time Factors; Vitamin D Deficiency