Impact of vitamin D receptor activity on experimental autoimmune prostatitis.

MOTRICH DR; VAN ETTEN E; DEPOVERE J; RIERA CM; RIVERO VE; MATHIEU C

JOURNAL OF AUTOIMMUNITY

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Año: 2009 vol. 32 p. 140 - 148

0896-8411

Chronic non bacterial prostatitis is a chronic inflammatory syndrome. Itsetiology and physiopathology are unclear and treatments are empirical andineffective in most cases. Autoimmunity has been proposed as an etiology. In the present report, we investigated the impact of vitamin D receptor silencing, byuse of VDR-KO NOD mice and the immune-modulating effect of the vitamin D3 analog TX527 on the development of Experimental Autoimmune Prostatitis in NOD mice.VDR-KO NOD mice developed a more aggressive form of autoimmune prostatitischaracterized by a greater lymphoproliferative response against prostate antigen in vitro (6.92+/-4.77 vs. 2.47+/-0.41 21 days after disease induction, p<0.05)and higher levels of specific INFgamma secretion (471+/-6 vs. 386+/-5pg/ml,p<0.01). This was accompanied in vivo by more severe lesions and augmentedmononuclear cell infiltration in the prostate gland. On the other hand, although analog-treated mice showed a significant reduction in the spleen T-cell specific proliferative response against prostate antigen in vitro, no effect on diseasedevelopment was observed. We conclude that vitamin D receptor modulation holdsthe promise of interfering with autoimmune prostatitis. Introduction of morepowerful analogs, or combinations with anti-T-cell reagents may representtherapeutic solutions for these group of patients