In this issue of BJU International, Gandaglia et al.  summarise the evidence supporting the role of chronic prostatic inflammation in the pathogenesis and progression of BPH. Briefly, one or more concomitant factors (bacterial infections, viruses, sexually transmitted organisms, dietary factors, hormones, autoimmune response and urine reflux) can stimulate an inflammatory reaction in prostatic tissue characterised by infiltration of T-lymphocytes, activation and up-regulation of pro-inflammatory cytokines, increased expression of potent stromal and epithelial growth factors (e.g. fibroblast growth factor, FGF-2) and consequently abnormal proliferation of prostatic cells. Moreover, local hypoxia plays an important role stimulating reactive oxygen species (ROS) release, neo-vascularisation processes and the production of other additional growth factors (vascular endothelial growth factor, interleukin 8, FGF-7, TGF-β and FGF-2). Interestingly, this mechanism is self-perpetuating, creating a local vicious cycle.
Available clinical data seems to emphasise the prevalence of chronic prostatic inflammation in BPH. Indeed, a sub-analysis of the REDUCE (REduction by DUtasteride of prostate Cancer Events) trial shows that in patients with BPH a chronic prostatic inflammation can be detected in 77% of patients who underwent prostate biopsies . Moreover, this study also showed a statistically and clinically significant correlation between chronic prostatic inflammation and LUTS severity, especially when the storage subscale was considered . As extensively described by Gandaglia et al. , other studies have shown a significant correlation between chronic prostatic inflammation and prostate volume and an increased risk of acute urinary retention.
Obviously, chronic prostatic inflammation can be histologically detected only in patients who undergo prostate biopsies for suspicion of prostate cancer. However, most patients with LUTS/BPH do not undergo a prostate biopsy. For this last category, the use of specific biomarkers correlated with chronic prostatic inflammation has been proposed as a potential alternative. Although interleukin 8 seems to be the most reliable and predictive surrogate marker to identify patients with chronic prostatic inflammation, its use is not yet popular, it is expansive and probably requires further clinical evaluation before introduction into daily clinical practice. In this context, the detection of prostatic calcifications can represent a simple ultrasound sign to suspect the presence of chronic prostatic inflammation. In patients aged >50 years, prostatic calcifications represent an age-related alteration of the prostatic fluid. Prostatic calcifications can produce an obstruction of the intraprostatic ducts stimulating an inflammatory response in prostatic tissue characterised by lymphocyte infiltration, cytokine activation and ROS release. This results in damage of epithelial and stromal prostatic cells and a subsequent process of wound healing consisting of stromal proliferation and excessive extracellular matrix production ; Fig. 1 summarises these mechanisms following prostatic duct obstruction (Fig. 1). I think that in patients with prostatic calcifications and severe LUTS (with predominant storage symptoms) the presence of chronic prostatic inflammation should be strongly considered.
Patients with high-grade prostatic inflammation seem to have a worse response to traditional medical therapy for LUTS/BPH (α-adrenergic blockers and 5α-reductase inhibitors) compared with patients without or with low-grade prostatic inflammation . Indeed, neither α-adrenergic blockers nor 5α-reductase inhibitors have an anti-inflammatory effect. Therefore, drugs commonly used for the treatment of non-neurogenic LUTS cannot influence the described chronic inflammatory status.
An anti-inflammatory effect on human prostate has been ascribed to the hexanic lipidosterolic extract of Serenoa repens. Specifically, in 2003 Vela Navarrete et al.  reported a significant reduction of interleukin 1 and TNF-α levels 3 months after Serenoa repens treatment compared with the placebo arm. Recently, Latil et al.  showed that Serenoa repens inhibits the expression of two key inflammatory mediators, monocyte chemoattractant protein 1/chemokine (C-C motif) ligand 2 (MCP-1/CCL2) and vascular cell adhesion molecule 1 (VCAM-1). Therefore, the use of this well-tolerated drug could be considered in patients with a demonstrated or suspicion of chronic inflammatory status. Obviously, well-conducted studies testing the anti-inflammatory effect of Serenoa repens in a clinical setting with patients with LUTS/BPH are mandatory to support a more evidence-based indication for this drug.
In conclusion, chronic prostatic inflammation seems to play a relevant role in the pathogenesis and progression of BPH. Therefore, this process should be taken more into consideration as a potential target for medical therapy. Hexanic lipidosterolic extract of Serenoa repens could have an interesting application in this context. However, more clinical data must be collected to confirm the anti-inflammatory effect of this plant extract.