Could inflammation be a key component in the progression of benign prostatic hyperplasia?

PURPOSE OF REVIEW: This review covers recent developments in the role of chronic inflammation in the pathogenesis and progression of benign prostatic hyperplasia (BPH). RECENT FINDINGS: A paper on the subanalysis of the Medical Therapy of Prostate Symptoms study highlighted the role of chronic inflammation in the progression of BPH as determined by the pathological tissue obtained in the 4.5-year study. It shows patients with inflammation had significantly larger prostates, higher serum prostate specific antigen and a greater risk of urinary retention. This follows several other in-situ studies which demonstrated that elevated expression of pro-inflammatory cytokines in BPH. IL-6, IL-8 and IL-17 may perpetuate chronic immune response in BPH and induce fibromuscular growth by an autocrine or paracrine loop or via induction of COX-2 expression. Immune reaction may be activated via Toll-like receptor signalling and mediated by macrophages and T cells. Conversely, anti-inflammatory factors such as macrophage inhibitory cytokine-1 decreased in symptomatic BPH tissues. Animal models provided evidence for the presence of unique T-cell subsets which may suppress autoimmunity in healthy Sprague-Dawley rats resistant to chronic nonbacterial prostatitis. SUMMARY: The pathogenesis of BPH is still unresolved, although chronic inflammation may play a significant role in disease progression. Further research is required to determine the putative (auto)antigen, the influence of infiltrating inflammatory cells on the stromal/epithelial cell crosstalk and a new classification of BPH quantifying local and systemic inflammatory/immune reactions in relation to clinical relevance. New treatments for BPH investigating these specific inflammatory pathways may arise as we learn more about the way they work.     

Rapid extracorporeal shock wave lithotripsy treatment after a first colic episode correlates with accelerated ureteral stone clearance

OBJECTIVES: To investigate the relationship between delay in extracorporeal shock wave lithotripsy (ESWL) after a first colic and subsequent time to complete stone clearance. METHODS: This prospective, non-randomized study included 94 patients treated with ESWL for unilateral solitary proximal ureteral stones after at least one episode of colic pain. Time between the first onset of colic pain and ESWL and stone clearance was recorded. The pretherapeutic degree of hydronephrosis has been assessed using ultrasound. RESULTS: Mean stone size was 7.9 +/- 2.3 mm and mean time before ESWL after a first colic was 93.4 +/- 143.5 h. At 3 months, 3 patients were lost to follow-up. In 76.9% of patients stones were completely cleared and a further 3.3% harbored residual fragments < or =3 mm. Delay in treatment after a first colic correlated with subsequent time to stone clearance (p < 0.0001). Mean time to stone clearance in patients treated within 24h was 6.4 +/- 6.3 days compared with 16.0 +/- 17.8 days for those treated later (p = 0.008). Maximum stone diameter correlated with time to stone clearance (p = 0.031), but the degree of hydronephrosis did not. CONCLUSIONS: Rapid ESWL after a first onset of colic pain resulted in accelerated stone clearance independent of the degree of hydronephrosis but had no impact on the need for auxiliary procedures.     

Proinflammatory effects of Staphylococcus aureus exotoxin B on nasal epithelial cells.

OBJECTIVE: The aim of this study was to evaluate the effects of Staphylococcus aureus exotoxin B (SE-B) on proinflammatory cytokine/chemokine releases in primary nasal epithelial cell cultures (NECC) of subjects with and without chronic rhinosinusitis (CRS). STUDY DESIGN AND SETTING: NECC (CRS: n = 14; Controls: n = 11) were stimulated with SE-B. Protein concentrations of interleukin-(IL)-1beta, IL-6, and IL-8 levels were measured in NECC supernatants by ELISA before (T0) and after 24 hr stimulation with SE-B (T1). RESULTS: T0: supernatants of the NECC of CRS patients contained significant lower levels of IL-8 (2.1 ng/ml) compared to Controls (IL-8: 6.2 ng/ml; P < 0.01). T1: SE-B induced a significant increase of IL-6 in NECC (P < 0.001). IL-1beta was not detectable. CONCLUSIONS: This is the first study evaluating the effects of exotoxins on NECC. SE-B showed proinflammatory effects on NECC. SIGNIFICANCE: Our data suggest that resident NECC are involved in immunological responses to Staphylococcus aureus toxins, supplementing the so-called "superantigen hypothesis" in CRS.     

Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

Background

Periprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin) deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice.

Methods

We used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE) particles in 10 C57BL/6J wild-type (WT) mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1), WT with UHMWPE particles (Group 2), Calca -/- mice without UHMWPE particles (Group 3), Calca -/- mice with UHMWPE particles (Group 4), Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5), and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6). Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP) + cells.

Results

Bone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin) increased significantly after CT substitution.

Conclusions

As anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.