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

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-gamma 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-gamma 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-gamma 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.

• Authors: Giuseppe Penna, Susana Amuchastegui, Chiara Cossetti, Francesca Aquilano, Roberto Mariani, Francesca Sanvito, Claudio Doglioni, Luciano Adorini
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 177 Issue 12 Pg. 8504-11 (Dec 15 2006) ISSN: 0022-1767 [Print] United States
• PMID: 17142748 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BXL628
• Receptors, Calcitriol
• Interferon-gamma
• Calcitriol

Topics

• Animals
• Apoptosis (drug effects)
• Autoimmune Diseases (drug therapy)
• CD4-Positive T-Lymphocytes (pathology)
• Calcitriol (administration & dosage, analogs & derivatives, pharmacology)
• Cell Count
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Immune System (pathology)
• Inflammation (prevention & control)
• Interferon-gamma (biosynthesis)
• Male
• Mice
• Mice, Inbred NOD
• Prostatitis (drug therapy, pathology)
• Receptors, Calcitriol (agonists)