Efficacy of a potent and safe vitamin D receptor agonist for the treatment of inflammatory bowel disease

Gilles Laverny, Giuseppe Penna, Stefania Vetrano, Carmen Correale, Manuela Nebuloni, Silvio Danese, Luciano Adorini

Research output: Contribution to journalArticlepeer-review


Deficiency in 1α,25-dihydroxyvitamin D3 (1,25D3) has been suggested as an important environmental factor for immuno-mediated disorders including inflammatory bowel diseases (IBD), comprising Crohn's disease and ulcerative colitis, both characterized by chronic intestinal inflammation. Administration of vitamin D receptor (VDR) agonists can ameliorate spontaneous and induced animal models of colitis, but hypercalcemia is a dose-limiting adverse event. Previous work in our laboratory has identified 1α,25(OH)2-16-ene-20-cyclopropyl-vitamin D3 (BXL-62) as a potent anti-inflammatory VDR agonist with a low calcemic activity. In the present study, we confirm the marked anti-inflammatory properties of BXL-62 and show its capacity to induce VDR primary response genes, like CYP24A1 and CAMP, at lower concentrations than 1,25D3, in PBMCs from IBD patients. Its higher anti-inflammatory potency compared to 1,25D3 was demonstrated by the significantly more potent inhibition in PBMCs and in lymphocyte-enriched lamina propria mononuclear cells of the pro-inflammatory cytokines TNF-α, IL-12/23p40, IL-6 and IFN-γ, both at mRNA and protein level. The therapeutic efficacy of intra-rectal administration of BXL-62 in experimental IBD is shown by its beneficial effects, significantly higher than 1,25D3, to induce recovery of clinical symptoms of colitis at normocalcemic doses in mice undergoing dextran sodium sulfate-induced colitis. These results confirm the therapeutic efficacy of VDR agonists in experimental colitis, and suggest BXL-62 as a promising compound for IBD treatment.

Original languageEnglish
Pages (from-to)49-58
Number of pages10
JournalImmunology Letters
Issue number1
Publication statusPublished - Jun 2010


  • Colitis
  • Inflammatory bowel disease
  • LPMC
  • TLR
  • VDR
  • Vitamin D

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy


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