Preclinical Therapy with Vitamin D3 in Experimental Encephalomyelitis: Efficacy and Comparison with Paricalcitol
Luiza Ayumi Nishiyama Mimura1, Thais Fernanda de Campos Fraga-Silva1, Larissa Ragozzo Cardoso de Oliveira1
1Department of Chemical and Biological Sciences, Institute of Biosciences, São Paulo State University (UNESP), Botucatu 18618-689, Brazil.
Abstract:
Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system (CNS). MS and its animal model called experimental autoimmune encephalomyelitis (EAE) immunopathogenesis involve a plethora of immune cells whose activation releases a variety of proinflammatory mediators and free radicals. Vitamin D3 (VitD) is endowed with immunomodulatory and antioxidant properties that we demonstrated to control EAE development. However, this protective effect triggered hypercalcemia. As such, we compared the therapeutic potential of VitD and paricalcitol (Pari), which is a non-hypercalcemic vitamin D analog, to control EAE. From the seventh day on after EAE induction, mice were injected with VitD or Pari every other day. VitD, but not Pari, displayed downmodulatory ability being able to reduce the recruitment of inflammatory cells, the mRNA expression of inflammatory parameters, and demyelination at the CNS. Lower production of proinflammatory cytokines by lymph node-derived cells and IL-17 by gut explants, and reduced intestinal inflammation were detected in the EAE/VitD group compared to the EAE untreated or Pari groups. Dendritic cells (DCs) differentiated in the presence of VitD developed a more tolerogenic phenotype than in the presence of Pari. These findings suggest that VitD, but not Pari, has the potential to be used as a preventive therapy to control MS severity.
Insights
Vitamin D3 (VitD) effectively controlled experimental autoimmune encephalomyelitis (EAE), a multiple sclerosis model, by reducing inflammation and demyelination. However, its analog paricalcitol did not show similar therapeutic benefits.
Area of Science:
- Neuroimmunology
- Demyelinating Diseases
- Immunomodulation
Background:
- Multiple sclerosis (MS) is a chronic central nervous system (CNS) demyelinating disease.
- MS immunopathogenesis involves immune cell activation, releasing proinflammatory mediators and free radicals.
- Vitamin D3 (VitD) possesses immunomodulatory and antioxidant properties, showing potential in controlling EAE, the animal model for MS.
Purpose of the Study:
- To compare the therapeutic potential of Vitamin D3 (VitD) and its non-hypercalcemic analog, paricalcitol (Pari), in controlling experimental autoimmune encephalomyelitis (EAE).
- To investigate the effects of VitD and Pari on immune cell activity, inflammation, and demyelination in the CNS.
Main Methods:
- Mice with induced EAE were treated with VitD or Pari every other day starting from day seven post-induction.
- Evaluated the recruitment of inflammatory cells, mRNA expression of inflammatory parameters, and demyelination in the CNS.
- Assessed proinflammatory cytokine production by lymph node cells and IL-17 by gut explants, alongside intestinal inflammation.
- Analyzed the phenotype of dendritic cells (DCs) differentiated in the presence of VitD or Pari.
Main Results:
- VitD treatment significantly reduced inflammatory cell recruitment, inflammatory gene expression, and demyelination in the CNS.
- EAE mice treated with VitD showed lower production of proinflammatory cytokines and IL-17, with reduced intestinal inflammation compared to untreated or Pari-treated groups.
- Dendritic cells differentiated with VitD exhibited a more tolerogenic phenotype than those differentiated with Pari.
Conclusions:
- Vitamin D3, but not paricalcitol, demonstrated significant immunomodulatory and protective effects in experimental autoimmune encephalomyelitis.
- VitD effectively reduced CNS inflammation and demyelination, suggesting its potential as a preventive therapy for multiple sclerosis.
