Treatment of experimental autoimmune prostatitis in nonobese diabetic mice by the vitamin D receptor agonist elocalcitol

Giuseppe Penna, Susana Amuchastegui, Chiara Cossetti, Francesca Aquilano, Roberto Mariani, Francesca Sanvito, Claudio Doglioni, Luciano Adorini

Research output: Contribution to journalArticle

Abstract

On the basis of on the marked inhibitory activity of the vitamin D receptor agonist Elocalcitol on basal and growth factor-induced proliferation of human prostate cells and on its potent anti-inflammatory properties, we have tested its capacity to treat experimental autoimmune prostatitis (EAP) induced by injection of prostate homogenate-CFA in nonobese diabetic (NOD) mice. Administration of Elocalcitol, at normocalcemic doses, for 2 wk in already established EAP significantly inhibits the intraprostatic cell infiltrate, leading to a profound reduction in the number of CD4+ and CD8 + T cells, B cells, macrophages, dendritic cells, and I-A g7-positive cells. Immunohistological analysis demonstrates reduced cell proliferation and increased apoptosis of resident and infiltrating cells. Significantly decreased production of the proinflammatory cytokines IFN-γ and IL-17 is observed in prostate-draining lymph node T cells from Elocalcitol-treated NOD mice stimulated by TCR ligation. In addition, Elocalcitol treatment reduces IFN-γ production by prostate-infiltrating CD4+ T cells and draining lymph node T cells specific for an immunodominant peptide naturally processed from prostate steroid-binding protein, a prostate-specific autoantigen. Finally, CD4+ splenic T cells from Elocalcitol-treated NOD mice show decreased ability, upon adoptive transfer into NOD.SCID recipients, to induce autoimmune prostatitis, paralleled by a reduced capacity to produce IFN-γ in response to prostate steroid-binding protein. The results indicate that Elocalcitol is able to interfere with key pathogenic events in already established EAP in the NOD mouse. These data show a novel indication for vitamin D receptor agonists and indicate that treatment with Elocalcitol may inhibit the intraprostatic inflammatory response in chronic prostatitis/chronic pelvic pain syndrome patients.

Original languageEnglish
Pages (from-to)8504-8511
Number of pages8
JournalJournal of Immunology
Volume177
Issue number12
Publication statusPublished - Dec 15 2006

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ASJC Scopus subject areas

  • Immunology

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