Chronic inflammation in the pathogenesis of benign prostatic hyperplasia.
Benign prostatic hyperplasia (BPH) is a common disorder affecting 50-80% of the aged male population. Androgens and age have been traditionally considered the main determinants of prostate enlargement, but in the last years a potentially important role of chronic inflammation in BPH pathogenesis has emerged. Bacterial and non-infectious chronic prostatitis could represent inciting factors leading to tissue hyperproliferation, possibly via the recently demonstrated antigen-presenting capacity of prostatic stromal cells, enabling them to induce and sustain intraglandular immune responses. The prostate growth-promoting chemokine IL-8 could represent a direct link between chronic prostate inflammation and autocrine/paracrine stromal cell proliferation, in agreement with its marked secretion induced in BPH stromal cells by a combination of Th1 and Th17 cell-derived inflammatory cytokines. BPH stromal cells express the vitamin D receptor (VDR), which is up-regulated by exposure to inflammatory stimuli. The non-hypercalcaemic VDR agonist elocalcitol, shown to arrest BPH development by decreasing the intra-prostatic androgen signalling without directly interfering with systemic androgen action, exerts immunoregulatory and anti-inflammatory properties in different prostatic pathology characterized by growth and inflammation. The mechanism of action of VDR agonists supports an important role of chronic inflammation in BPH pathogenesis and strengthens the concept of these agents as a therapeutic option for pharmacological treatment of BPH.
Fibbi
B
B
Andrology Unit, Department of Clinical Physiopathology, University of Florence, Florence, Italy.
Penna
G
G
Morelli
A
A
Adorini
L
L
Maggi
M
M
D000728:Androgens / Q000502:physiology / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002117:Calcitriol / Q000031:analogs & derivatives; D018925:Chemokines / Q000627:therapeutic use; D002908:Chronic Disease; D016207:Cytokines / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology*; D016209:Interleukin-8 / Q000627:therapeutic use; D008297:Male; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D011472:Prostatitis / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D018167:Receptors, Calcitriol / Q000819:agonists / Q000378:metabolism; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
D000728:Androgens; D000893:Anti-Inflammatory Agents; C487049:BXL628; D018925:Chemokines; D016207:Cytokines; D016209:Interleukin-8; D018167:Receptors, Calcitriol; D002117:Calcitriol