Chronic inflammation in benign prostatic hyperplasia: Pathophysiology and treatment options.
benign prostatic hyperplasia
chronic inflammation
microbiome
pelvic ischemia
treatments
urine reflux
Journal
International journal of urology : official journal of the Japanese Urological Association
ISSN: 1442-2042
Titre abrégé: Int J Urol
Pays: Australia
ID NLM: 9440237
Informations de publication
Date de publication:
27 Jun 2024
27 Jun 2024
Historique:
received:
16
02
2024
accepted:
05
06
2024
medline:
27
6
2024
pubmed:
27
6
2024
entrez:
27
6
2024
Statut:
aheadofprint
Résumé
Benign prostatic hyperplasia, a prevalent condition in aging men, is characterized by the proliferation of prostatic epithelial and stromal cells, which leads to bladder outlet obstruction and the exacerbation of lower urinary tract symptoms. There is increasing evidence that chronic prostatic inflammation contributes to the pathogenesis and progression of benign prostatic hyperplasia. This review explores the complex relationship between chronic inflammation and benign prostatic hyperplasia, focusing on the underlying mechanisms, clinical implications, and current therapeutic approaches. The pathophysiology of benign prostatic hyperplasia is multifaceted, involving factors such as hormonal changes, hypoxia, urine reflux into prostatic ducts and stroma, autoimmune responses, and infection-induced inflammation. Inflammatory cytokines, particularly interleukin-17 and interleukin-8, may play key roles in tissue remodeling and smooth muscle contraction within the prostate, thereby influencing benign prostatic hyperplasia progression. Current therapies for benign prostatic hyperplasia include α1-blockers, phosphodiesterase 5 inhibitors, 5α-reductase inhibitors, and plant-based treatments (e.g., pollen extract). These therapies aim to alleviate symptoms by reducing prostatic inflammation, improving blood flow, and inhibiting hormonal pathways involved in prostatic enlargement. However, patients with chronic prostatic inflammation often experience more severe lower urinary tract symptoms and may be resistant to conventional treatments. This resistance has prompted the exploration of alternative therapies targeting inflammation. Chronic prostatic inflammation plays a central role in the pathogenesis and severity of benign prostatic hyperplasia. An understanding of its mechanisms will enable the development of more effective treatments to improve the quality of life among patients with benign prostatic hyperplasia.
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 The Author(s). International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.
Références
Sakai Y, Kobayashi M. Lymphocyte ‘homing’ and chronic inflammation. Pathol Int. 2015;65:344–354.
Furman D, Campisi J, Verdin E, Carrera‐Bastos P, Targ S, Franceschi C, et al. Chronic inflammation in the etiology of disease across the life span. Nat Med. 2019;25:1822–1832.
Inamura S, Shinagawa T, Hoshino H, Sakai Y, Imamura Y, Yokoyama O, et al. Appearance of high endothelial venule‐like vessels in benign prostatic hyperplasia is associated with lower urinary tract symptoms. Prostate. 2017;77:794–802.
Chen L, Zhang M, Liang C. Chronic prostatitis and pelvic pain syndrome: another autoimmune disease? Arch Immunol Ther Exp. 2021;69:24.
Nickel JC, Elhilali M, Vallancien G, Group A‐OS. Benign prostatic hyperplasia (BPH) and prostatitis: prevalence of painful ejaculation in men with clinical BPH. BJU Int. 2005;95:571–574.
Marker PC, Donjacour AA, Dahiya R, Cunha GR. Hormonal, cellular, and molecular control of prostatic development. Dev Biol. 2003;253:165–174.
Nickel JC, Roehrborn CG, O'Leary MP, Bostwick DG, Somerville MC, Rittmaster RS. The relationship between prostate inflammation and lower urinary tract symptoms: examination of baseline data from the REDUCE trial. Eur Urol. 2008;54:1379–1384.
Andriole G, Bostwick D, Brawley O, Gomella L, Marberger M, Tindall D, et al. Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial. J Urol. 2004;172:1314–1317.
Li J, Li Y, Cao D, Huang Y, Peng L, Meng C, et al. The association between histological prostatitis and benign prostatic hyperplasia: a single‐center retrospective study. Aging Male. 2022;25:88–93.
Kobayashi M, Mitoma J, Nakamura N, Katsuyama T, Nakayama J, Fukuda M. Induction‐of‐peripheral‐lymph‐node‐addressin‐in‐human‐gastric‐mucosa‐infected‐by‐helicobacter. Proc Natl Acad Sci USA. 2004;101:17807–17812.
Kobayashi M, Hoshino H, Masumoto J, Fukushima M, Suzawa K, Kageyama S, et al. GlcNAc6ST‐1‐mediated decoration of MAdCAM‐1 protein with L‐selectin ligand carbohydrates directs disease activity of ulcerative colitis. Inflamm Bowel Dis. 2009;15:697–706.
De Nunzio C, Kramer G, Marberger M, Montironi R, Nelson W, Schröder F, et al. The controversial relationship between benign prostatic hyperplasia and prostate cancer: the role of inflammation. Eur Urol. 2011;60:106–117.
Penna G, Fibbi B, Amuchastegui S, Cossetti C, Aquilano F, Laverny G, et al. Human benign prostatic hyperplasia stromal cells as inducers and targets of chronic immuno‐mediated inflammation. J Immunol. 2009;182:4056–4064.
Kobayashi H, Zha X, Nagase K, Inamura S, Taga M, Aoki Y, et al. Phosphodiesterase 5 inhibitor suppresses prostate weight increase in type 2 diabetic rats. Life Sci. 2022;298:120504.
Nickel JC, Roehrborn CG, Castro‐Santamaria R, Freedland SJ, Moreira DM. Chronic prostate inflammation is associated with severity and progression of benign prostatic hyperplasia, lower urinary tract symptoms and risk of acute urinary retention. J Urol. 2016;196:1493–1498.
Akiho H, Tokita Y, Nakamura K, Satoh K, Nishiyama M, Tsuchiya N, et al. Involvement of interleukin‐17A‐induced hypercontractility of intestinal smooth muscle cells in persistent gut motor dysfunction. PLoS One. 2014;9:e92960.
Govindaraju V, Michoud MC, Ferraro P, Arkinson J, Safka K, Valderrama‐Carvajal H, et al. The effects of interleukin‐8 on airway smooth muscle contraction in cystic fibrosis. Respir Res. 2008;9:76.
Yokoyama O, Yusup A, Oyama N, Aoki Y, Miwa Y, Akino H. Improvement in bladder storage function by tamsulosin depends on suppression of C‐fiber urethral afferent activity in rats. J Urol. 2007;177:771–775.
Funahashi Y, Takahashi R, Mizoguchi S, Suzuki T, Takaoka E, Ni J, et al. Bladder overactivity and afferent hyperexcitability induced by prostate‐to‐bladder cross‐sensitization in rats with prostatic inflammation. J Physiol. 2019;597:2063–2078.
Bajic P, Dornbier RA, Doshi CP, Wolfe AJ, Farooq AV, Bresler L. Implications of the genitourinary microbiota in prostatic disease. Curr Urol Rep. 2019;20:34.
Takezawa K, Fujita K, Matsushita M, Motooka D, Hatano K, Banno E, et al. The firmicutes/Bacteroidetes ratio of the human gut microbiota is associated with prostate enlargement. Prostate. 2021;81:1287–1293.
Mukaida N, Okamoto S, Ishikawa Y, Matsushima K. Molecular mechanism of interleukin‐8 gene expression. J Leukoc Biol. 1994;56:554–558.
Kozlowski R, Kershen R, Siroky M, Krane R, Azadzoi K. Chronic ischemia alters prostate structure and reactivity in rabbits. J Urol. 2001;165:1019–1026.
Wang L, Yang JR, Yang LY, Liu ZT. Chronic inflammation in benign prostatic hyperplasia: implications for therapy. Med Hypotheses. 2008;70:1021–1023.
Funahashi Y, Majima T, Matsukawa Y, Yamamoto T, Yoshida M, Gotoh M. Intraprostatic reflux of urine induces inflammation in a rat. Prostate. 2017;77:164–172.
Pascal LE, Dhir R, Balasubramani GK, Chen W, Hudson CN, Srivastava P, et al. Claudin‐1 down‐regulation in the prostate is associated with aging and increased infiltration of inflammatory cells in BPH. Am J Clin Exp Urol. 2021;9:53–64.
Feng Li LEP, Wang K, Zhou Y, Balasubramani GK, O'Malley KJ, Dhir R, et al. Transforming growth factor Beta 1 impairs benign prostatic luminal epithelial cell monolayer barrier function. Am J Clin Exp Urol. 2020;25:9–17.
Vickman RE, Aaron‐Brooks L, Zhang R, Lanman NA, Lapin B, Gil V, et al. TNF is a potential therapeutic target to suppress prostatic inflammation and hyperplasia in autoimmune disease. Nat Commun. 2022;13:2133.
Lokant MT, Naz RK. Presence of PSA auto‐antibodies in men with prostate abnormalities (prostate cancer/benign prostatic hyperplasia/prostatitis). Andrologia. 2015;47:328–332.
Kouiavskaia DV, Southwood S, Berard CA, Klyushnenkova EN, Alexander RB. T‐cell recognition of prostatic peptides in men with chronic prostatitis/chronic pelvic pain syndrome. J Urol. 2009;182:2483–2489.
Yeh JC, Hiraoka N, Petryniak B, Nakayama J, Ellies LG, Rabuka D, et al. Novel sulfated lymphocyte homing receptors and their control by a Core1 extension beta 1,3‐N‐acetylglucosaminyltransferase. Cell. 2001;105:957–969.
Nickel JC, True LD, Krieger JN, Berger RE, Boag AH, Young ID. Consensus development of a histopathological classificationsystem for chronic prostatic inflammation. BJU Int. 2001;87:797–805.
Irani J, Levillain P, Goujon JM, Bon D, Dore B, Aubert J. Inflammation in benign prostatic hyperplasia: correlation with prostate specific antigen value. J Urol. 1997;157:1301–1303.
Liao X, Tang Z, Ai J, Xu H, Zhang S, Liu L, et al. Detection of prostatic inflammation from peripheral lymphocyte count and free/Total PSA ratio in men with LUTS/BPH. Front Pharmacol. 2020;11:589.
Appiya Santharam M, Khan FU, Naveed M, Ali U, Ahsan MZ, Khongorzul P, et al. Interventions to chronic prostatitis/chronic pelvic pain syndrome treatment. Where are we standing and what's next? Eur J Pharmacol. 2019;857:172429.
Nickel JC, Downey J, Johnston B, Clark J, Group CPR. Predictors of patient response to antibiotic therapy for the chronic prostatitis/chronic pelvic pain syndrome: a prospective multicenter clinical trial. J Urol. 2001;165:1539–1544.
Nickel JC, Roehrborn C, Montorsi F, Wilson TH, Rittmaster RS. Dutasteride reduces prostatitis symptoms compared with placebo in men enrolled in the REDUCE study. J Urol. 2011;186:1313–1318.
Vignozzi L, Cellai I, Santi R, Lombardelli L, Morelli A, Comeglio P, et al. Antiinflammatory effect of androgen receptor activation in human benign prostatic hyperplasia cells. J Endocrinol. 2012;214:31–43.
Kamijo T, Sato S, Kitamura T. Effect of cernitin pollen‐extract on experimental nonbacterial prostatitis in rats. Prostate. 2001;49:122–131.
Matsukawa Y, Naito Y, Funahashi Y, Ishida S, Fujita T, Tochigi K, et al. Comparison of cernitin pollen extract vs tadalafil therapy for refractory chronic prostatitis/chronic pelvic pain syndrome: a randomized, prospective study. Neurourol Urodyn. 2020;39:1994–2002.
Cai T, Verze P, La Rocca R, Palmieri A, Tiscione D, Luciani LG, et al. The clinical efficacy of pollen extract and vitamins on chronic prostatitis/chronic pelvic pain syndrome is linked to a decrease in the pro‐inflammatory cytokine interleukin‐8. World J Mens Health. 2017;35:120–128.
Nickel JC, Shoskes DA, Wagenlehner FM. Management of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS): the studies, the evidence, and the impact. World J Urol. 2013;31:747–753.
Bates SM, Hill VA, Anderson JB, Chapple CR, Spence R, Ryan C, et al. A prospective, randomized, double‐blind trial to evaluate the role of a short reducing course of oral corticosteroid therapy in the treatment of chronic prostatitis/chronic pelvic pain syndrome. BJU Int. 2007;99:355–359.