Treatment with Vitamin D/MOG Association Suppresses Experimental Autoimmune Encephalomyelitis

Abstract

Experimental autoimmune encephalomyelitis (EAE) is an animal model to study multiple sclerosis (MS). Considering the tolerogenic effects of active vitamin D, we evaluated the therapeutic effect of myelin oligodendrocyte glycoprotein (MOG) associated with active vitamin D in EAE development. EAE was induced in female C57BL/6 mice by immunization with MOG emulsified with Complete Freund’s Adjuvant plus Mycobacterium tuberculosis. Animals also received two intraperitoneal doses of Bordetella pertussis toxin. One day after immunization, mice were treated with 0,1μg of 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) every other day during 15 days (on days 1, 3, 5, 7, 9, 11, 13 and 15). MOG (150μg) was co-administered on days 3 and 11. The administration of 1,25(OH) 2D3 or MOG determined significant reduction in EAE incidence and in clinical scores. When MOG was associated with 1,25(OH) 2D3 the animals did not develop EAE. Spleen and central nervous system (CNS) cell cultures from this group produced less IL-6 and IL-17 upon stimulation with MOG in comparison to the EAE control group. In addition, this treatment inhibited dendritic cells maturation in the spleen and reduced inflammatory infiltration in the CNS. The association of MOG with 1,25(OH) 2D3 was able to control EAE development.

Liposome-Based Immunotherapy Against Autoimmune Diseases: Therapeutic Effect on Multiple Sclerosis

“…MOG [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] peptide (YRSPFSRVVHLYRNGK, Immunostep, Salamanca, Spain), >95% pure, was chosen because it is a target epitope in MS patients [18]. Liposomes were composed of 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (sodium salt) (DOPS, Lipoid, Steinhausen, Switzerland) and 1,2-didodecanoyl-snglycero-3-phosphocholine (DLPC, Lipoid), and cholesterol (CH, Sigma Aldrich, MO, USA).…”

“…Lipids were dissolved in chloroform and the solvent was removed by evaporation under vacuum and nitrogen. The lipids were hydrated with the appropriate buffer (phosphate-buffered saline [PBS], 0.5 mg/ml solution of MOG [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] peptide) and the liposomes obtained were homogenized to 1 μm by means of an extruder (Lipex Biomembranes, Vancouver, Canada). Encapsulation efficiencies (EE) were calculated according to the equation EE (%) = [(C peptide, total -C peptide, out )/C peptide, total ] × 100, where C peptide, total is the initial MOG 40-55 peptide concentration and C peptide, out is the concentration of nonencapsulated peptide.…”

“…The current treatments are systemic immunointerventions, with important side effects [15]. In this context, PS-liposomes loaded with an autoantigen of the disease, the myelin-oligodendrocyte glycoprotein peptide 40-55 (MOG [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] ), have been proved as a potential antigen-specific therapy for MS patients.…”

“…It is induced by the administration of myelin antigens. The most frequent EAE model used is C57BL/6 mice injected with the MOG [40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] peptide [16,17], and it has been the major tool to understand the mechanism involved in MS pathogenesis, as well as to test therapies for the human disease. To determine the effect of a therapy in EAE, three different approaches can be used: preventive (before immunization), preclinical (postimmunization) and therapeutic (after the onset of the disease) [17].…”

Therapeutic and Prophylactic Potential of Vitamin D for Multiple Sclerosis

“…Confirming this hypothesis, we recently demonstrated that a combined therapy with MOG + VitD blocked EAE development. This elevated efficacy was correlated with reduced production of IL-6 and IL-17 by spleen and CNS cell cultures stimulated with MOG, reduced splenic DC maturation, and also a striking decline in CNS inflammation [119] (Figure 2). Figure 2.…”