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-Ag7-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.

Hypovitaminosis D is associated with lower urinary tract symptoms and benign prostate hyperplasia in type 2 diabetes

“…Some studies have demonstrated that chronic prostatic inflammation might be responsible for several biological changes, leading to prostate overgrowth (Nickel et al, 2005) and for prostatitis-like symptoms associated with BPH in at least 20% of patients (Adorini & Penna, 2008). Upregulation of several proinflammatory cytokines has been described in BPH, in particular of interleukin (IL)-2, IFN-c, IL-15, IL-8, and IL-17, suggesting the hypothesis that BPH may represent an 'immune inflammatory' disease (Penna et al, 2006). Vitamin D could therefore oppose the BPH through its immunoregulatory/ anti-inflammatory properties.…”

Vitamin D Deficiency in Axial Spondyloarthritis is Associated With Higher Disease Activity

“…15 Treatment with vitamin D receptors agonists decreased IL-17 production in mice. 14,16 There are many factors associated with active axSpA that could result in a vitamin D deficient state. These include the presence of subclinical bowel inflammation, associated with active axSpA, that may impair absorption; although dietary contribution to vitamin D status is small.…”

Topically Applied 1,25-Dihydroxyvitamin D3 Enhances the Suppressive Activity of CD4+CD25+ Cells in the Draining Lymph Nodes

“…The greatest reductions in proliferation were observed at 4 and 7 days post 1,25(OH) 2 D 3 administration (Fig. 2D) [22][23][24]. To determine whether this occurred in our model, cytokine levels were examined in culture supernatants obtained 92 h after the coculture of APC with CD4 ϩ cells from the SDLN of treated mice.…”