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Keywords:

  • benign prostatic hyperplasia (BPH);
  • chronic prostatic inflammation;
  • LUTS severity;
  • acute urinary retention;
  • prostatic calcifications;
  • biomarkers

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Conclusions
  7. Conflict of Interest
  8. References
  • Several different stimuli may induce chronic prostatic inflammation, which in turn would lead to tissue damage and continuous wound healing, thus contributing to prostatic enlargement.
  • Patients with chronic inflammation and benign prostatic hyperplasia (BPH) have been shown to have larger prostate volumes, more severe lower urinary tract symptoms (LUTS) and a higher probability of acute urinary retention than their counterparts without inflammation.
  • Chronic inflammation could be a predictor of poor response to BPH medical treatment. Thus, the ability to identify patients with chronic inflammation would be crucial to prevent BPH progression and develop target therapies.
  • Although the histological examination of prostatic tissue remains the only available method to diagnose chronic inflammation, different parameters, such as prostatic calcifications, prostate volume, LUTS severity, storage and prostatitis-like symptoms, poor response to medical therapies and urinary biomarkers, have been shown to be correlated with chronic inflammation.
  • The identification of patients with BPH and chronic inflammation might be crucial in order to develop target therapies to prevent BPH progression. In this context, clinical, imaging and laboratory parameters might be used alone or in combination to identify patients that harbour chronic prostatic inflammation.

Abbreviations
AUR

acute urinary retention

CD

cluster of differentiation

CPSI

Chronic Prostatitis Symptoms Index

FGF

fibroblast growth factor

ICOS

inducible T-cell co-stimulator

IL

interleukin

MCP-1

monocyte chemotactic protein-1

MTOPS

Medical Therapy of Prostate Symptoms (study)

REDUCE

REduction by DUtasteride of prostate Cancer Events (trial)

ROS

reactive oxygen species

US

ultrasonography/ultrasound

WBC

white blood cell

Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Conclusions
  7. Conflict of Interest
  8. References

BPH represents the most commonly diagnosed urological disease in men after the fifth decade [1]. Although BPH aetiology remains uncertain in some aspects, several mechanisms have been proposed to be involved in the pathogenesis and progression of BPH [2]. First, ageing represents the most significant risk factor for the developing of BPH and the compliant of LUTS. In ageing men, an interference in growth factors pathway occurs and a significant tissue-remodelling process takes place, leading to prostatic enlargement [3]. Second, hormonal alterations have been proposed to be involved in BPH pathogenesis and progression. Indeed, the development of BPH requires the presence of testicular androgens, and BPH tissue has higher dihydrotestosterone activity than normal prostate gland tissue [4, 5]. Additionally, insulin resistance with secondary hyperinsulinaemia has been proposed to be involved in the development of BPH [6, 7]. Third, a role of increased sympathetic nerve activity has also been proposed [7-9]. Finally, in the last few years the role of prostatic inflammation as a crucial part of BPH pathogenesis and progression has emerged. Interestingly, it has been hypothesised that inflammatory infiltrate leads to tissue damage and to a chronic process of wound healing that might subsequently determinate prostatic enlargement [2, 7, 10, 11].

The aim of the present review was to critically analyse the role of chronic inflammation in the pathogenesis and progression of BPH. Moreover, we evaluated new tools for the identification of patients with chronic prostatic inflammation in the clinical setting.

Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Conclusions
  7. Conflict of Interest
  8. References

A literature review searching Medline, Embase, and Web of Science databases was performed. The search strategy included the terms: ‘benign prostatic hyperplasia’, ‘pathogenesis’, ‘progression’, ‘pathophysiology’, ‘LUTS severity’, ‘prostate volume’, ‘prostate calcifications’, ‘metabolic syndrome’, ‘chronic prostatic inflammation’, ‘inflammatory infiltrate’ and ‘biomarkers’ alone or in combination. We limited out search to English-language articles published between January 2005 and December 2012. In addition, cited references from the selected articles and from review articles retrieved in our search were used to identify manuscripts that were not included in the previous search (Fig. 1).

figure

Figure 1. Flowchart showing the search strategy for the identification of studies included in the review.

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Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Conclusions
  7. Conflict of Interest
  8. References

The Role of Chronic Prostate Inflammation in the Pathogenesis of BPH

Among several hormonal and vascular mechanisms proposed to be involved in the pathogenesis and progression of BPH, the role of chronic inflammation has emerged during the last few years.

The prostate is an immunocompetent organ and it is normally populated by a small number of inflammatory cells (i.e. T and B lymphocytes, macrophages and mast cells) [12]. In this context, the immune response of the prostate is primarily T-cell mediated and this class of lymphocytes represents >90% of prostatic lymphocytes, both in the epithelial and stromal compartments [13]. Particularly, regulatory T-cells (cluster of differentiation 4 [CD-4]) are mainly located to the fibromuscular stroma, while cytotoxic T-cell (CD-8) infiltrates are distributed more around the peri-glandular area [13].

The origin of chronic prostate inflammation is still unclear and it might reside in several concomitant stimuli. Interestingly, different sources of prostatic inflammation have been proposed, including bacterial infections (Escherichia coli), viruses (human papilloma virus, human herpes simplex virus and cytomegalovirus), sexually transmitted organisms (Neisseria gonorrhea, Treponema pallidum, Chlamydia trachomatis and Trichomonas vaginalis), dietary factors, hormones, autoimmune response and urine reflux [14].

The persistence of one or the combination of two or more of these stimuli might lead to chronic prostate inflammation. In this context, Steiner et al. [15, 16] investigated the immunophenotypical and biological properties of chronic inflammatory prostate infiltrates. In their studies, the Authors elegantly showed an increase of macrophages and lymphocytes (CD-45) in inflammatory infiltrates. Particularly, 70–80% of these inflammatory cells were CD-3 T lymphocytes, while 10–15% were CD-19 and CD-20 B lymphocytes [15, 16]. Interestingly, a reversed CD-4 : CD-8 pattern has also been reported in inflammatory areas, where most T lymphocytes expressed CD-4 [15, 16].

Prostate tissue inflammatory patterns have been also widely assessed in patients with BPH [15-19]. Figure 2 shows the distribution of chronic inflammation and inflammatory elements (i.e. lymphocytes, macrophages, neutrophils, cytokines and reactive oxygen species ([ROS]) in BPH tissues. Robert et al. [19] recently characterised the inflammatory infiltrate in a large cohort of patients surgically treated for BPH. Interestingly, 81% of patients had T lymphocytes infiltrates (CD-3), 52% B cells (CD-20) and 82% macrophages markers (CD-163) in BPH tissues [19]. Thus, T-cells represented the major component of the inflammatory infiltrate seen within the prostatic gland. Moreover, an increased expression of B lymphocytes and macrophages was reported. These antigen-presenting cells play an important role in the activation of T lymphocytes and in the subsequent onset of an inflammatory state [19].

figure

Figure 2. Distribution of chronic inflammation and inflammatory elements (i.e. lymphocytes, macrophages, neutrophils, cytokines and ROS) in BHP tissues.

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The chronic inflammatory condition may contribute to tissue injury, activating cytokines release and increasing the concentration of growth factors, creating a local vicious cycle. In this context, the up-regulation of pro-inflammatory cytokines has been widely reported in prostatic tissues of patients with BPH [10, 15, 16, 20-22]. Particularly, several studies showed an increase in the expression of interleukin (IL)-15 in stromal cells [20], IL-17 in infiltrating T-cells [15], interferon-γ in basal and stromal cells [21], and IL-8 in epithelial cells [22]. Interestingly, IL-8 has been proposed as a link between chronic prostate inflammation and the development of BPH. This cytokine is produced by epithelial prostate cells and can induce the expression of fibroblast growth factor (FGF)-2, a potent stromal and epithelial growth factor and consequently promote the abnormal proliferation of prostatic cells [22].

Local hypoxia may also play a role in the pathophysiology of BPH leading to release of ROS, which can promote neo-vascularisation and growth factors release (i.e. vascular endothelial growth factor, IL-8, FGF-7, TGF-β and FGF-2) [23]. These growth factors may interact not only with inflammatory cells, but also with the stromal and epithelial cells of the prostate, leading to prostatic enlargement.

Concluding, all these data support the hypothesis that tissue damage, hypoxia and chronic process of wound healing lead to a persistent process of stimulation of stromal and epithelial prostatic tissues, potentially resulting in BPH (Fig. 3).

figure

Figure 3. Representation of the role of chronic prostatic inflammation on BPH pathogenesis. Several stimuli lead to tissue damage, inflammatory response and the chronic process of wound healing, resulting in prostate enlargement.

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The Role of Chronic Prostatic Inflammation in the Progression of BPH

Although the role of chronic prostatic inflammation on BPH pathogenesis is still not completely understood several studies have investigated the role of inflammation on BPH progression. Table 1 summarises the characteristics of clinical studies evaluating the role of inflammation on BPH progression [19, 24-29].

Table 1. Characteristics of studies evaluating the role of chronic inflammation on BPH progression
ReferenceStudy populationMean (sd) age, yearsDefinition of chronic inflammationDefinition of BPH progressionLimitationsStrengthsOutcome/commentsStatistical significance (P value)
  1. IHC, immunohistochemistry; NA, not available; Statistical significance (P value): statistical significance of the association between chronic prostatic inflammation and BPH progression; n.s., not statistically significant.

Nickel et al. 2008 [24]8224 patients included in the REDUCE trial68.1 (6.1)Histological evaluation of prostate biopsyIPSSStudy entry criteria selected older men and excluded patients with severe LUTS or clinically prostatitisNumber of patients included, use of validated questionnaires (IPSS), differentiation between acute and chronic inflammationChronic inflammation was associated with prostate volume, total and irritative IPSS<0.001
Robert et al. 2009 [19]282 patients treated with surgery for complicated and/or symptomatic BPH70Combination of six cytological parameters and five markers on IHCIPSS and prostate volumePatients with high-grade inflammation more commonly underwent TRUS-guided prostate biopsy than those in the low-grade groupUse of cytological and histological parameters to assess prostatic inflammationPatients with chronic inflammation had higher prostate volumes, IPSS and a higher frequency of open prostatectomy≤0.02
Tuncel et al. 2005 [25]92 patients undergoing TURPNAReview of prostatic specimens for chronic inflammationAURRetrospective design, small number of patients includedInflammation assessed in the pathological specimen after surgery, detailed medical history availableAUR was 3.03 times higher in BPH patients with chronic inflammation than those patients without0.01
Roehrborn et al. 2005 [26]544 patients included in the MTOPS studyNAHistological evaluation of prostate biopsyAURWeak correlation at baseline between inflammation and BPHLarge cohort of patients affected by LUTS not requiring surgical treatmentInflammation was associated with higher prostate volume, serum PSA and higher risk of AUR0.003
Mishra et al. 2007 [27]374 patients undergoing TURPNAStromal infiltration composed of lymphocytes and plasma cells with neutrophils and macrophagesAURRetrospective design, patients treated with TURP for AUR had a higher rate of catheterisation than those undergoing surgery for LUTSUTI assessed 1–2 weeks before surgeryThe association between urinary retention and chronic inflammation was stronger than that with prostate volume0.001
Kwon et al. 2010 [28]82 patients undergoing prostate biopsyNAClassification of the extent of chronic inflammation in two groups: low- vs high-gradeIPSS improvement after medical therapies (i.e. α-adrenergic blockers and 5α-reductase inhibitors)Low number of patients includedPatients were evaluated with IPSS at baseline and 1, 3, 6, and 12 months after medical treatment for BPHPatients in the low-grade group had higher and long-lasting IPSS improvement compared with those in the high-grade groupn.s.
Kim et al. 2012 [29]225 patients undergoing TURP68.7 (7.5)Classification of pathological specimen into three grades according to the degree of chronic inflammationTotal IPSS and storage IPSS sub-scoreLow number of patients, lack of inclusion of men not receiving surgeryPathological examination of surgical specimens, prostatic symptoms assessed with IPSSTotal IPSS and storage IPSS sub-score increased with increasing chronic inflammation. However, this study failed to show an association between prostatic calcification and chronic inflammation≤0.03

Correlation between Chronic Inflammation and LUTS Severity

In their pioneering study, Nickel et al. [24] evaluated the relationship between prostatic inflammation, prostate volume and the degree of LUTS. They evaluated 8224 men aged 50–75 years with BPH undergoing prostate biopsy and included in the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial. Patients were classified according to the presence of acute and chronic inflammation at biopsy. Interestingly, 77.6% of patients presented with chronic inflammation. This study showed a positive association between inflammation and prostate volume, indeed patients with chronic inflammation at biopsy had higher volumes than those without inflammation (46.5 vs 43.4 mL, respectively; P < 0.001). Older age and higher degree of chronic inflammation were also significantly associated with higher IPSS (8.8 vs 8.2, respectively; P < 0.001). Specifically, patients with chronic inflammation had significantly higher storage IPSS sub-scores (namely, frequency, nocturia, urgency, precipitancy, urge incontinence; at 4.3 vs 4.1, respectively; P < 0.001) [24]. Although statistically significant the association between IPSS and chronic inflammation was clinically small. In this context, the findings of this study are limited by the study entry criteria that selected older men (i.e. 50–75 years) and excluded patients with severe LUTS (i.e. IPSS ≥25) [24]. Indeed, including patients with higher IPSS might have resulted in a greater association between inflammation and LUTS severity.

Robert et al. [19] assessed the degree of prostatic inflammation using cytological and immunohistochemical parameters in 282 patients treated with surgery for complicated or symptomatic BPH. Interestingly, the grade of prostatic inflammation was strongly associated with LUTS severity, and patients with chronic inflammation had higher IPSS than those without inflammation (21 vs 12, respectively; P = 0.02). Moreover, prostate volume was significantly higher in patients with high-grade inflammatory pattern (77 vs 62 mL; P = 0.002). Additionally, patients in the high-grade group more commonly underwent open prostatectomy than those in the low-grade group. This finding may also be related to the association between prostate volume and chronic intraprostatic inflammation. Unfortunately, patients included in the high-grade group more commonly underwent TRUS-guided prostate biopsy than those with low-grade inflammation (37.6 vs 23.9%; P < 0.02) [19]. In this context, bacteriological contamination related to the biopsy might have induced a local immune response.

Despite these limitations, all these data showed a statistically and clinically significant association between chronic inflammation and LUTS severity, supporting the hypothesis that inflammation could at least contribute to the clinical progression of BPH [19, 24].

Relationship between Chronic Inflammation and Acute Urinary Retention (AUR)

Several studies evaluated the relationship between chronic prostatic inflammation and the risk of AUR in patients affected by BPH [25-27]. Particularly, Tuncel et al. [25] investigated the role of inflammation on urinary retention aetiology. The study included 92 patients undergoing TURP or open prostatectomy for BPH. Patients were classified in two groups according to the cause of surgery: Group 1 included patients with AUR and Group 2 included patients with LUTS. Severe prostatic inflammation was defined as destructive infiltration of both glandular and stromal elements by inflammatory cells. Interestingly, prostatic inflammation was significantly higher in Group 1 than Group 2 (54.7 vs 28.9%, respectively; P = 0.01) and the risk of AUR was higher in patients with inflammation [25].

In a sub-analysis of the Medical Therapy of Prostate Symptoms (MTOPS) study, Roehrborn et al. [26] highlighted the role of chronic inflammation on BPH progression. In their study, the Authors evaluated prostate biopsy of 1198 patients with BPH. Inflammation was seen in 544 patients (45.4%), and in the vast majority of these patients (94.3%) it was described as chronic. Additionally, this study confirmed that inflammation was associated with higher prostate volume and higher serum PSA values. Interestingly, patients with inflammation at biopsy were at higher risk of AUR than those without inflammation (5.6 vs 0%, respectively; P = 0.003). Moreover, there was a trend towards higher clinical progression rates in men with inflammation compared with those without inflammation [26].

Similarly, Mishra et al. [27] clearly showed that prostatic inflammation was associated with a higher risk of AUR. They evaluated 374 patients with BPH treated with TURP for either AUR or LUTS. While chronic intraprostatic inflammation was found in 70% of men with AUR, only 45% of patients treated because of LUTS showed inflammation at final histology (P < 0.001). Additionally, prostates with inflammation were found to be larger than glands without inflammation [27]. These findings are limited by the fact that patients undergoing surgery for AUR had a higher rate of catheterisation before TURP as compared with those with LUTS. The presence of a urinary catheter might have resulted in an immune response and thus in prostatic inflammation. However, the duration of catheterisation was not associated with the presence of prostatic inflammation at final histology [27].

Taken together, the results of these studies support the role of chronic inflammation as a risk factor for AUR in patients with BPH [25-27].

Effects of Chronic Inflammation on Medical Treatment Efficacy

Recently, Kwon et al. [28] investigated how chronic intraprostatic inflammation affected the response to BPH medical treatments. The study included 82 patients with BPH who underwent prostate biopsy. A single pathologist was used to classify the extent of chronic inflammation into four grades, which were then categorised into two groups: low- and high-grade prostatic inflammation. The Authors compared total, voiding and storage IPSS and quality-of-life scores between the two groups at baseline as well as at 1, 3, 6, and 12 months after medical therapy (i.e. α-adrenergic blockers and 5α-reductase inhibitors). Even in the absence of a statistical significance, there was a trend towards higher and long-lasting IPSS improvement after medical therapy in patients in the low-grade inflammation group, as compared with those in the high-grade group. Moreover, while no patient in the low-grade group underwent surgery, 9.1% of patients in the high-grade group were treated with TURP for AUR or insufficient therapeutic response [28].

Although these data need to be confirmed in further, larger studies, these preliminary results suggest that high-grade intraprostatic inflammation might be considered as a predictor of poor response to medical treatment in men with BPH. Presence of such an inflammatory pattern might identify those ‘difficult to treat’ patients in whom combined therapies might be considered to improve patient outcomes.

How to Identify Patients Affected by BPH with Chronic Prostate Inflammation?

As previously reported, patients with BPH and chronic inflammation might have a higher risk of symptoms progression and a lower rate of response to medical treatment [19, 24-28]. Currently, the histological examination of prostate biopsies remains the only available method to diagnose chronic prostatic inflammation. As prostate biopsies cannot be proposed to all patients with BPH, less invasive tools are needed to determine the risk of harbouring prostatic chronic inflammation. In this context, clinical (i.e. LUTS severity and poor response to medical treatment), imaging (i.e. prostate volume and prostatic calcifications at ultrasonography [US]), and laboratory (i.e. urine, serum and seminal plasma biomarkers) parameters could be used alone or in combination to identify this class of patients.

Interestingly, although laboratory biomarkers are promising tools for identifying patients affected by chronic prostatic inflammation, they are not yet routinely available in clinical practice. However, LUTS severity, response to medical treatment, prostate volume and calcifications detected by US are easily detectable parameters that might help the physician in the identification of patients with prostatic inflammation.

Severity and Type of LUTS

Chronic prostatic inflammation has been related to several clinical parameters that might depict BPH progression [19, 24-28]. These parameters may be useful to identify patients with BPH with a high probability of harbouring prostatic inflammation. In this context, Nickel et al. [24] reported a relationship between the degree of chronic inflammation and LUTS severity in the REDUCE population. Particularly, they highlighted the correlation between chronic inflammation and storage symptoms (namely, frequency, nocturia, urgency, precipitancy, urge incontinence) [24]. Moreover, Robert et al. [19] showed a strong correlation between histological inflammation and IPSS, confirming previous findings.

Another study by Nickel et al. [30] evaluated the relationship between symptoms of prostatitis and histological inflammation recorded on prostate biopsy in the REDUCE population. In this study, the Chronic Prostatitis Symptoms Index (CPSI) was used to assess prostatitis-like symptoms (namely, pain and burning sensation, dribbling and hesitant urination, urgency, pain or discomfort of the penis and testicles and painful ejaculations). Interestingly, total CPSI score and sub-scores for urinary symptoms and quality of life were significantly greater in men with chronic inflammation than in those without inflammation. Thus, severity and type of LUTS (namely, the presence of storage and prostatitis-like symptoms) might be used to identify patients with chronic prostatic inflammation [30]. Furthermore, patients with BPH not responding to medical treatment might be considered at higher risk of chronic, significant, intra-prostatic inflammation [28].

Metabolic Syndrome, Prostatic Enlargement and Prostate Inflammation

Recently, it has been shown that patients affected by metabolic syndrome are at higher risk of BPH [9]. In this context, metabolic syndrome is associated with increased levels of C-reactive protein, IL-1β, IL-6, IL-8 and TNF-α, reflecting a systemic inflammatory status [31, 32]. Interestingly, chronic inflammation might represent a common link between metabolic syndrome and BPH development. Indeed, cytokines and macrophage infiltration related to obesity and metabolic syndrome might contribute to the chronic inflammatory pattern in patients with BPH, resulting in wound-healing and consequent proliferation of prostatic tissues [33-35]. Thus, men with metabolic syndrome should be considered at higher risk of harbouring chronic prostatic inflammation. Moreover, metabolic syndrome, alone or in association with other clinical parameters, might be useful to identify patients with BPH and chronic prostatic inflammation.

Prostatic Calcifications and Prostate Volume

Prostatic calcifications are common in men with BPH and their incidence increases with age [36-38]. Interestingly, calcifications were also seen in 47.2% of younger men aged <50 years with urological complaints [38]. In this context, Shoskes et al. [36] evaluated the incidence and significance of calcifications in 130 patients with chronic pelvic pain syndrome. In these patients, calcifications detected at TRUS were significantly associated with greater inflammation and longer symptoms duration [36]. Similarly, Geramoutsos et al. [39] screened 1374 young men and reported 101 (7.4%) cases of prostatic stones. Interestingly, they found that patients with larger stones were at higher risk of developing LUTS or prostatitis [39].

It could be speculated that in young patients alterations in the prostatic fluid related to infections or inflammatory diseases might result in prostatic calcifications, which may obstruct intraprostatic ducts and subsequently enhance the inflammatory process. The incidence of prostatic calcifications is ≈90% in patients aged >50 years with LUTS [38, 39], thus we can hypothesise that they can be involved in the pathogenesis of BPH as well. Particularly, calcifications could be the expression of previous infections leading to a chronic inflammatory process, with higher risk of subsequent BPH development over time [40].

Thus, the evidence of prostatic calcification at US might be an easily detectable and useful marker of the intraprostatic chronic inflammatory state.

In contrast with this hypothesis, a recent study by Kim et al. [29] evaluating 225 patients who underwent TURP for BPH did not show any correlation between severity of chronic prostatic inflammation and calculus type detected by preoperative TRUS. However, these findings are limited by the heterogeneous definition of prostatic inflammation and by the few patients included in each group [29]. Moreover, the study included only patients who received TURP. Thus, these findings are not applicable to all patients with BPH. In this context, further larger prospective studies are needed to clarify the role of prostatic calculi detected at US in the pathogenesis of inflammation and in the identification of patients affected by BPH with associated chronic inflammation.

Additionally, as several studies reported an association between inflammation and prostate volume [19, 24, 26], this parameter could also be useful to identify patients with inflammation. Indeed, US evaluation of prostate volume is commonly performed in the management of BPH [41].

Biomarkers

Several studies evaluated the correlation between serum, urinary and seminal plasma biomarkers and the presence and degree of chronic inflammation at prostate biopsy [42-46].

Historically, white blood cell (WBC) count in prostatic secretion has been considered as ‘the marker’ of prostatitis. However, it has been shown that WBC count had poor sensitivity and it could not detect all patients with BPH with prostatic inflammation [42]. Thus, WBC count is no longer considered the optimal marker of inflammation, providing only limited clinically useful information.

Conversely, other markers such as IL-8 seminal plasma level might be considered more reliable in the identification of prostatic inflammation. Indeed, this pro-inflammatory cytokine, produced by prostate epithelial cells, has been proposed as a link between chronic inflammation and the subsequent development of BPH [22, 47]. In this context, Penna et al. [43] evaluated seminal plasma levels of eight cytokines and nine chemokines in 83 men. Interestingly, they concluded that IL-8 seminal plasma levels were the most reliable and predictive surrogate marker to diagnose prostatic inflammation [43]. These results were recently confirmed by Liu et al. [42]. In their well conducted study, the association between IL-8 in prostatic secretion and chronic inflammation was assessed in 44 patients undergoing surgery for BPH. This study clearly showed that the levels of IL-8 in patients with BPH and chronic prostatitis were significantly higher than those in patients with BPH only [42]. Thus, IL-8 seminal plasma levels might be a useful marker of chronic prostatic inflammation in patients with BPH.

Other markers might also be useful to reliably identify the presence of prostatic inflammation. Recently, Robert et al. [48] collected tissue samples from 90 patients with BPH undergoing surgery in order to identify urinary biomarkers for the identification of chronic inflammation. The Authors showed that the urinary levels of inducible T-cell co-stimulator (ICOS), a protein involved in cell-signalling, immune response and cell proliferation, were significantly associated with maximum uroflowmetry and post-void residual urine volume. As this protein is expressed by T-cells and is released as a soluble form [49], its urinary levels might potentially be used for the diagnosis of chronic inflammation [48]. However, further studies are needed to confirm these findings.

Fujita et al. [45] found that increased monocyte chemotactic protein-1 (MCP-1) levels in prostatic secretions correlated with prostate volume, as well as with the expression of the macrophage marker CD-68. Thus, the Authors hypothesised that MCP-1 and macrophages might play a role in the development of prostatic inflammation and in the pathogenesis of BPH. As MCP-1 levels in expressed prostatic secretions are easily assessable with ELISA, this protein is a potential marker to detect chronic inflammation and could be considered a therapeutic target in patients with BPH [45, 50]. Indeed, an in vitro study by Latil et al. [50] elegantly reported that phytotherapeutic agents, such as the hexanic lipidosterolic extract of Serenoa Repens, inhibit MCP-1 expression by human prostate cells, blocking key steps of the inflammation process [50].

Finally, a correlation between serum PSA levels and chronic prostatic inflammation in patients with BPH has been hypothesised. Song et al. [46] investigated the association between the extent of histological inflammation and the level of serum PSA in 454 patients undergoing surgery for BPH. In their retrospective study, the Authors showed that the aggressiveness of inflammatory infiltration was a significant contributor to elevated PSA levels [46]. Thus, patients with BPH with high levels of serum PSA might be considered at higher risk of harbouring chronic inflammation.

Conclusions

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Conclusions
  7. Conflict of Interest
  8. References

A variety of evidence supports the role of chronic prostatic inflammation in the pathogenesis and progression of BPH. The association between inflammatory infiltration and clinical parameters reflecting BPH progression has been widely assessed. Additionally, chronic inflammation might be considered a predictor of poor response to medical treatment. Thus, the identification of patients with chronic inflammation plays a crucial role in order to develop target therapies to prevent BPH progression. In this context, clinical, imaging and laboratory parameters might be used alone or in combination to identify patients that harbour chronic intraprostatic inflammation.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Methods
  5. Results
  6. Conclusions
  7. Conflict of Interest
  8. References
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