Differential therapeutic effect of vitamin D and Paricalcitol on experimental autoimmune encephalomyelitis.

Author(s)

Luiza Ayumi Nishiyama Mimura

• Document type: Doctoral Thesis
• Press: Botucatu. 2019-04-29.
• Institution: Universidade Estadual Paulista (Unesp). Instituto de Biociências. Botucatu
• Defense date: 2019-03-01
• Advisor: Alexandrina Sartori

Abstract

Multiple sclerosis (MS) is a chronic and demyelinating disease of the central nervous system (CNS). MS and experimental autoimmune encephalomyelitis (EAE) immunopathogenesis involve T lymphocytes, macrophages and microglial cells whose activation will release a plethora of pro-inflammatory mediators and free radicals. Vitamin D3 (VitD) and its analog Paricalcitol (Pari) are endowed with immunomodulatory activity and are used in autoinflammatory and autoimmune diseases. Recently, we demonstrated that VitD was able to control EAE development when administered soon after disease induction. Therefore, the aim of this work was to compare the therapeutic potential of VitD and Pari to control EAE development and also to evaluate if this therapeutic approach is efficient to control ongoing disease. C57BL/6 mice immunized with myelin oligodendrocyte glycoprotein emulsified with complete Freund’s adjuvant were intraperitoneally treated with VitD or Pari (0,1ug/animal, 15 every other day). Therapy was initiated 7 days post induction when the autoimmune response was already established or 10 days post induction when the first symptoms appeared. VitD or Pari therapy started ten days after induction did not determine protection. Therapy started seven days after disease induction brought forth unexpected results. VitD reduced disease severity, decreased MHCII, NLRP3 and CX3CR1 expression at the CNS, increased the percentage of neutrophils in the lungs and increased the permeability of the intestinal barrier. Pari therapy had no major protective effect; however it reduced CX3CR1 mRNA expression in the CNS, decreased expression of RORc in lung eluted cells and increased IL-6 and IL-17 production in the intestine. We conclude that VitD, but not its analog Pari, is effective to control EAE even if administered at the pre-clinical stage. Additional experiments are already being performed to elucidate the mechanisms involved in this differential effect of VitD and its analog. (AU)

• FAPESP's process: 15/06706-8 - Vitamin D, paricalcitol, glibenclamide and clofazimine: therapeutic and immunomodulatory potential in experimental autoimmune encephalomyelitis
• Grantee: Luiza Ayumi Nishiyama Mimura
• Support Opportunities: Scholarships in Brazil - Doctorate