Inhibition of Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D3

Frank Mattner, Simona Smiroldo, Francesca Galbiati, Marc Muller, Pietro Di Lucia, Pietro L. Poliani, Gianvito Martino, Paola Panina-Bordignon, Luciano Adorini

Research output: Contribution to journalArticlepeer-review

Abstract

1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibits production of IL-12, a cytokine involved in the development of Th1 cells and in the pathogenesis of Th1-mediated autoimmune diseases. Here, we show that 1,25(OH)2D3 and a non-hypercalcemic analogue are selective and potent inhibitors of Th1 development in vitro and in vivo without inducing a deviation to the Th2 phenotype. Administration of 1,25(OH)2D3 or its analogue prevents chronic-relapsing experimental allergic encephalomyelitis (CR-EAE) induced by the myelin oligodendrocyte glycoprotein (MOG) peptide 35-55 (MOG35-55) in Biozzi AB/H mice. The inhibition of EAE induction is associated with a profound reduction of MOG35-55-specific proliferation and Th1 cell development. Importantly, the non-hypercalcemic analogue also provides long-term protection from EAE relapses induced by immunization with spinal cord homogenate when administered for a short time at symptom onset or even after the first peak of disease. Neuropathological analysis shows a reduction of inflammatory infiltrates, demyelinated areas and axonal loss in brains and spinal cords of treated mice. These resuls indicate that inhibition of IL-12-dependent Th1 cell development is associated with effective treatment of CR-EAE and suggest the feasibility of an approach based on low molecular weight inhibitors of IL-12 production in the treatment of multiple sclerosis.

Original languageEnglish
Pages (from-to)498-508
Number of pages11
JournalEuropean Journal of Immunology
Volume30
Issue number2
DOIs
Publication statusPublished - 2000

Keywords

  • Chronic-relapsing experimentall allergic encephalomyelitis
  • Th1
  • Vitamin D

ASJC Scopus subject areas

  • Immunology

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