Inflammation In Prostate Tissue Research Articles

Fabrication and application of targeted ciprofloxacin nanocarriers for the treatment of chronic bacterial prostatitis

Pathogenic bacteria cause chronic bacterial prostatitis (CBP). CPB is characterized by urinary tract infection and persistence of pathogenic bacteria in prostatic secretion. Owing to poor blood supply to the prostate gland and limited drug penetration, CBP treatment is difficult. Transferosomes are ultradeformable vesicles for nanocarrier applications, which have become an important area of nanomedicine. Such carriers are specifically targeted to the pathological area to provide maximum therapeutic efficacy. It consists of a lipid bilayer soybean lecithin phosphatidylcholine (PC), an edge activator Tween 80 with various ratios, and a chloroform/methanol core. Depending on the lipophilicity of the active substance, it can be encapsulated within the core or among the lipid bilayer. Due to their exceptional flexibility, which enables them to squeeze themselves through narrow pores that are significantly smaller than their size, they can be a solution. One formulation (Cipro5 PEG) was selected for further in vitro analysis and was composed of phosphatidylcholine (PC), Tween 80, and polyethylene glycol-6 stearate (PEG-6 stearate) in a ratio of 3:3:1 in a chloroform/methanol mixture (1:2 v/v). In vitro, the results showed that PEGylated transferosomes had faster drug release, higher permeation, and increased bioavailability. The transferosomes were quantified with a particle size of 202.59 nm, a zeta potential of-49.38 mV, and a drug entrapment efficiency of 80.05%. The aim of this study was to investigate drug targeting. Therefore, Monoclonal antibody IgG was coupled with Cipro5 PEG, which has specificity and selectivity for conjugated nanoparticles. In vivo, a total of twenty-five adult Wistar rats were obtained and randomly divided into 5 groups, each of 5 rats at random: the control group, blank group, positive control group, Cipro 5PEG group, and Cipro 5PEG coupled with IgG antibody group. The cytokines levels (IL-1β, IL-8, and TNF-α) in the serum were detected by analysis kits. Compared with the control group, treatment with Cipro 5PEG coupled with the IgG antibody could significantly inhibit cytokines, according to histological analysis. Cipro 5PEG, coupled with the IgG antibody group, reduced prostate tissue inflammation. Hence, our results show a promising approach to delivering antibiotics for the targeted therapy of CBP.

CD8 T cells are dispensable for experimental autoimmune prostatitis induction and chronic pelvic pain development.

Chronic Pelvic Pain Syndrome or Chronic Prostatitis (CPPS/CP) is the most prevalent urologic affliction among young adult men. It is a challenging condition to treat, which significantly decreases patient quality of life, mostly because of its still uncertain aetiology. In that regard, an autoimmune origin is a prominent supported theory. Indeed, studies in patients and in rodent models of Experimental Autoimmune Prostatitis (EAP) have provided compelling evidence suggesting a key role of CD4 Th1 cells in disease pathogenesis. However, the implication of other prominent effectors of the immune system, such as CD8 T cells, has yet to be studied. We herein analyzed the induction of prostatitis and the development of chronic pelvic pain in EAP using CD8 T cell-deficient animals. We found similarly elevated PA-specific immune responses, with high frequencies of specific IFNg+CD4+ and IL17+CD4+ T cells in prostate draining lymph nodes from PA-immunized either CD8 KO or wild type animals with respect to controls. Moreover, these peripheral immune responses were paralleled by the development of significant chronic pelvic pain, and accompanied by prostate histological lesions, characterized by hemorrhage, epithelial cell desquamation, marked periglandular leukocyte infiltration, and increased collagen deposition in both, PA-immunized CD8 KO and wild type animals. As expected, control animals did not develop prostate histological lesions. Our results indicate that CD8 T cells do not play a major role in EAP pathogenesis and chronic pelvic pain development. Moreover, our results corroborate the previous notion that a CD4 Th1 associated immune response drives the induction of prostate tissue inflammation and the development of chronic pelvic pain.

Perioperative changes in ganglioside monosialodihexosylganglioside (GM3) molecular species for benign prostatic hyperplasia: a preliminary report.

Benign prostatic hyperplasia (BPH) progresses with age and is associated with chronic inflammation. We focused on the relationship between BPH and ganglioside monosialodihexosylganglioside (GM3), a sialic acid-containing glycosphingolipid that is involved in chronic inflammation. GM3 molecular species would have a significant role in regulating inflammatory processes. In this prospective study, preoperative and postoperative serum samples were obtained from patients who underwent holmium laser enucleation of the prostate (HoLEP) for BPH. Preoperative and postoperative measurements of serum GM3 species were performed one month before and three months after HoLEP. Twenty-three patients were included in the study. The average patient age was 75 years, and the average prostate volume was 66 mL. The average weight of the surgically resected prostate tissue was 42 g. At three months after HoLEP, the serum concentration of GM3 species was found to have decreased after HoLEP compared with the preoperative concentration of GM3 species. Six GM3 species such as d18:1-17:0 [C17 acyl chain (-17:0) linked to a C18 sphingosine base with a double bond (d18:1-) by an amide linkage], were significantly reduced. The sample size was small; therefore, this study showed only preliminary results and could not evaluate prostate tissue inflammation. This study showed that the serum concentrations of several GM3 species, which indicate chronic inflammation, may be significantly reduced after BPH surgery.

PD02-11 THE EXTENT OF CHRONIC PROSTATIC INFLAMMATION WAS NEGATIVELY AND POSITIVELY CORRELATED WITH THE DURATION OF ALPHA-1 BLOCKERS AND 5 ALPHA REDUCTASE INHIBITORS BEFORE SURGICAL TREATMENT

You have accessJournal of UrologyCME1 Apr 2023PD02-11 THE EXTENT OF CHRONIC PROSTATIC INFLAMMATION WAS NEGATIVELY AND POSITIVELY CORRELATED WITH THE DURATION OF ALPHA-1 BLOCKERS AND 5 ALPHA REDUCTASE INHIBITORS BEFORE SURGICAL TREATMENT So Inamura, Tomochika Shinagawa, Hisato Kobayashi, Manami Tsutsumiuchi, Masaya Seki, Minekatsu Taga, Masato Fukushima, Osamu Yokoyama, and Naoki Terada So InamuraSo Inamura More articles by this author , Tomochika ShinagawaTomochika Shinagawa More articles by this author , Hisato KobayashiHisato Kobayashi More articles by this author , Manami TsutsumiuchiManami Tsutsumiuchi More articles by this author , Masaya SekiMasaya Seki More articles by this author , Minekatsu TagaMinekatsu Taga More articles by this author , Masato FukushimaMasato Fukushima More articles by this author , Osamu YokoyamaOsamu Yokoyama More articles by this author , and Naoki TeradaNaoki Terada More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003219.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Alpha 1 blockers (ABs) and 5 alpha-reductase inhibitors (5ARIs) have been used for the medical treatment of benign prostatic hyperplasia (BPH) and the patients resistant to these therapies receive surgical treatment. We previously reported that the extent of chronic prostatic inflammation was positively correlated with the obstruction of BPH patients in pressure flow study (Inamura et al. Prostate 2018). This study investigated the correlation of the duration of ABs and 5ARIs with the extent of chronic inflammation by evaluating the expression levels of high endothelial venule (HEV) in prostate tissue. METHODS: Tissue samples were obtained from BPH patients who underwent transurethral resection of the prostate (TURP) or holmium enucleation of the prostate (HoLEP). All the patients received pressure flow study before the surgery. HEV is associated with the migration of lymphocytes and is used as a marker of chronic inflammation. The magnitude of prostatic inflammation was quantified histologically by the ratio of HEV and endothelial cells using the immunohistochemistry of MECA-79 and CD34. The type and duration of medical treatment before surgery were examined on medical records. The correlation of MECA-79/CD34 ratio with the duration of ABs and 5ARIs was evaluated. RESULTS: In 148 patients, 143 patients (97%) received ABs and 33 patients (22%) received 5ARIs adding to ABs. The median duration ABs was 14 months, and the median duration of 5ARIs was 7 months. The duration of ABs was significantly negatively correlated with Bladder Outlet Obstruction Index (BOOI) in pressure flow study (correlation coefficient=-0.270 p=0.029). The duration of ABs was significantly negatively correlated with MECA-7/CD34 ratio (correlation coefficient=-0.194, p=0.030). However, the duration of 5ARIs was positively correlated with MECA-7/CD34 ratio (correlation coefficient=0.501, p=0.001). CONCLUSIONS: These results indicated that the patients who received longer treatment by ABs before surgery had lower level of obstruction and lower extent of chronic prostatic inflammation. However, the patients who received longer treatment of 5ARIs had higher extent of chronic prostatic inflammation. The long-term therapy by 5ARIs might have potential to enhance chronic inflammation in prostate tissue. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e72 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information So Inamura More articles by this author Tomochika Shinagawa More articles by this author Hisato Kobayashi More articles by this author Manami Tsutsumiuchi More articles by this author Masaya Seki More articles by this author Minekatsu Taga More articles by this author Masato Fukushima More articles by this author Osamu Yokoyama More articles by this author Naoki Terada More articles by this author Expand All Advertisement PDF downloadLoading ...

Association between interleukin-6 and lower urinary tract symptoms of benign prostatic hyperplasia

ObjectiveTo evaluate the association between IL-6 in prostatic tissue/blood sample and BPH-LUTS, so as to preliminarily discover an indicator of inflammation that could show the severity of LUTS. Patients and methodsThe prostatic tissues and blood samples were collected from 56 patients who underwent transurethral plasmakinetic resection of the prostate (TUPKRP). The association between IL-6 detected on prostatic tissues/blood sample and LUTS parameters, including international prostate symptom score (IPSS), peak flow rate (Qmax) and urodynamic parameters were analyzed with SPSS version 18.0, and p-value <0.05 was chosen as the criterion for statistical significance. ResultsThe TPSA and prostate volume (PV) were found to be higher in the inflammation group (p=0.021, 0.036). There was a positive association between prostate tissue inflammation and LUTS ([IPSS, storage symptoms score (SSS), voiding symptoms score (VSS), p<0.05], [Qmax, p=0.025], [obstruction, p=0.027] and [AUR, p=0.018]). The level of serum IL-6 was significantly higher in inflammatory group (p=0.008). However, no differences were observed in different degrees of inflammation (p=0.393). The level of IL-6 in prostatic tissue significantly increased with the degree of inflammation (p<0.001), and the intensity of IL-6 expression was statistically correlative with the degree of inflammation (p<0.001). The IL-6 expression in prostatic tissue was statistically relevant with IPSS (p=0.018) and SSS (p=0.012). ConclusionIL-6 expression in prostatic tissue is associated with storage IPSS, suggesting chronic inflammation might contribute to storage LUTS.

A rat study model of depression-driven chronic prostatitis by modulating the PI3K/Akt/mTOR network.

Depression and chronic prostatitis (CP) are two common diseases that affect the human population worldwide. Clinically, it has been demonstrated that andrological patients often simultaneously suffer from depression and CP. Prior investigations have established that depression acts as an independent risk factor for CP. Herein, we explored the correlation between depression and CP using bioinformatics tools and through animal experiments. The potential targets and signalling pathways involved in depression and CP were predicted using bioinformatics tool, while depression in the rat model was established through chronic restraint stress. The expression of the related proteins and mRNA was assessed by Western blotting and real-time fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR). Relative to those in the control rats, the protein contents of PI3K, p-Akt, and p-mTOR were lower in the model rats (p < 0.05). Similarly, the transcript levels of PI3K, Akt, and mTOR was also relatively lower in the model rats (p < 0.05). And PI3K/Akt agonists reduced inflammation in rat prostate tissue, accompanied by significant increases in the transcript and protein expression levels of PI3K, Akt, and mTOR. Thus, we proposed that depression model rats may induce CP as a result of mediation by the negative regulation of the PI3K/Akt/mTOR signalling network.

The role of COVID-19 in prostate tissue inflammation: first pathological evidence.

According to current studies, COVID-19 might have an impact on semen quality. Therefore, SARS-CoV-2 may affect other traits of male reproductive system, including the prostate. Thus, we recruited patients who experienced COVID-19 infection in-between prostate biopsy and radical prostatectomy and compared prostate samples inflammation, measured with IRANI score, to those who did not. Indeed, we recruited 20 patients, aged 69 (62–73) years, finding no difference between the 10 patients with COVID-19 infection and the others in IRANI score and all its sub-scores. Hence, according to our exploratory and limited results, COVID-19 infection might have no gross effect on prostate inflammation.

Immune Cell Proinflammatory Microenvironment and Androgen-Related Metabolic Regulation During Benign Prostatic Hyperplasia in Aging.

To review the role of inflammation in the occurrence and development of benign prostatic hyperplasia (BPH), we searched PubMed for the latest published articles up to February 2021 using the following key words: “benign prostatic hyperplasia”, “inflammation”, “pathogenesis” and “disease development”. Articles were obtained and reviewed to provide a systematic review of the current progress of the role of inflammation in the pathogenesis and progression of BPH. Inflammation contributes to the initiation and maintenance of unregulated cell proliferation and is closely related to the occurrence and development of BPH. Its action pathways include tissue damage and subsequent chronic healing, autoimmunity, and coaction with androgens. During the progression of inflammation, macrophages, interleukin-8 (IL-8), interleukin-1 (IL-1) and other inflammatory-related substances aggregate locally and cause BPH through various biochemical pathways. At the same time, BPH can also counteract inflammation to expand its scope and aggravate the situation. Inflammation can independently affect the development of BPH in a variety of ways, and it can also interact with androgens. In the course of treatment, early intervention in the occurrence and development of inflammation in prostate tissue can slow down the progression of BPH. The combination of standard therapies and anti-inflammatory measures may provide valuable new ideas for the treatment of BPH.

Combined treatment with dihydrotestosterone and lipopolysaccharide modulates prostate homeostasis by upregulating TNF-α from M1 macrophages and promotes proliferation of prostate stromal cells

Androgens and chronic inflammation, which play essential roles in the development of benign prostatic hyperplasia (BPH), are considered to be important factors in disorders of prostate homeostasis. These two factors may lead to pathological hyperplasia in the prostate transition zone of patients with BPH. However, few studies have examined the mechanism of how dihydrotestosterone (DHT) affects chronic inflammation in prostate tissue during the progression of BPH. This study examined the performance of DHT in lipopolysaccharide-treated M1 macrophages and the subsequent effects on the proliferation of prostate stromal and epithelial cells. We found that DHT increased secretion of the pro-inflammatory factor tumor necrosis factor (TNF)-α from M1 macrophages differentiated from THP-1 cells. The supernatant of M1 macrophages promoted the proliferation of WPMY-1 prostate stromal cells by upregulating B-cell lymphoma-extra large (Bcl-xL) and cellular Myc (c-Myc) levels by activating TNF-α-mediated nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. Moreover, this supernatant increased the expression of androgen receptor in WPMY-1 cells, which was TNF-α-independent. Additionally, TNF-α protein expression was significantly higher in patients with BPH and a large prostate volume than that in those with a small prostate volume. Further analysis showed that higher serum testosterone combined with prostate-specific androgen concentrations was related to TNF-α expression. This study suggests that DHT modulates the inflammatory environment of BPH by increasing TNF-α expression from lipopolysaccharide-treated M1 macrophages and promotes the proliferation of prostate stromal cells. Targeting TNF-α, but not DHT, may be a promising strategy for patients with BPH.

Association between Inflammation and Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia.

To evaluate the association between inflammation in prostatic tissue/serum sample and BPH-LUTS Patients and methods: The prostatic tissue and serum sample were collected from 183 patients who underwent transurethral plasmakinetic resection of the prostate (TUPKRP). The association between inflammation detected on prostatic tissues/ serum sample and LUTS related parameters, including International Prostate Symptom Score (IPSS) and peak flow rate (Qmax) were analyzed with SPSS version 13.0, and P-value <0.05 was chosen as the criterion for statistical significance. There was a positive association between prostate tissue inflammation and LUTS. The differences of IPSS, VSS and SSS were seen with the increasing in grade of prostate tissue inflammation (P<.001; .001; =.014, respectively). Qmax and IPSS 12months after surgery were better in no inflammation group (P=.016; .031).Logistic regression analysis revealed a statistically association between the NEUT%?NLR and prostate tissue inflammation (P=.010; .004), but ROC curve showed the NEUT%, NEUT and NLR area under curve (.526; .452; .513, respectively) were calculated as <0.600. Patients with Qmax over 7.12 had more WBC count in peripheral blood (7.56±1.77 VS 6.37±1.86, P=.026). The NLR was significantly higher in the group of IPSS over 20 and AUR presence (P=.018; .017).The NEUT%, LYMPH%, LYMPH and NLR showed a statistically significance in different obstruction classification (P=.047; .046; .028; .014, respectively). There was correlation between chronic Inflammation and LUTS related to BPH. The patient without inflammation could acquire more sustained and steady relief than those with inflammation in LUTS related to BPH after TUPKRP.

Novel Treatment of Experimental Autoimmune Prostatitis by Nanoparticle-Conjugated Autoantigen Peptide T2.

The exact etiology and pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still unknown, as a result, available therapeutic options for patients are far from satisfactory. Therefore, there is a need to develop a valid therapeutic approach that can ameliorate the manifestations of CP/CPPS. Fifty male C57BL/6 mice were randomly divided into five groups of ten mice each. All groups except naïve were subcutaneously injected with 0.2ml of T2 plus complete Freund adjuvant (CFA) on day 0 and 14 to generate valid CP/CPPS model. After successful CP/CPPS induction, model group was injected with 0.2ml of normal saline while PLGA, PLGA-OVA, and PLGA-T2 groups were administered intravenously with 0.2ml mixture of PLGA, PLGA-OVA, and PLGA-T2, respectively. Voiding behavior, pain threshold, and hematoxylin and eosin staining were used to assess micturition habits, pain intensity as well as prostate inflammation. Additionally, TNF-α, CRP, and IL-10 levels in plasma were measured by using ELISA kits. Mice administered with PLGA-T2 showed higher pain threshold, lower urine frequencies, mild edema, and inflammation in prostate tissue in comparison to other groups. Moreover, the expression of TNF-α and CRP levels was markedly decreased while IL-10 expression was increased in the PLGA-T2 treatment group as compared to the other groups. Our results showed that nanoparticles conjugated with autoantigen novel peptide T2 could successfully alleviate or even heal CP/CPPS to some extent in mice. This study provides an easy, useful, and economic tool for ameliorating the manifestations of CP/CPPS that will improve the therapeutic approaches.

081 Testosterone replacement therapy is able to reduce prostate inflammation in men with BPH, metabolic syndrome and hypogonadism: preliminary results from a randomized placebo-controlled clinical trial

BPH results from prostate tissue inflammation, which frequently occurs in men with metabolic syndrome (MetS). MetS is often associated with low testosterone (T). Recent evidence shows that low, rather than high, T levels are associated with BPH/lower urinary tract symptoms (LUTS). The aim of the study was to evaluate if T replacement therapy (TRT) for 6 months in BPH men with MetS and low T, is able to improve LUTS and prostate inflammation (as assessed by ultrasound and gene expression in prostate tissue). 120 men in waiting list for BPH surgery and diagnosed with MetS were enrolled in the clinical trial. According to total T (TT) and calculated free T (cFT), they were categorized into eugonadal (TT≥12 nmol/L and cFT≥225 pmol/L; n=48) and hypogonadal men (TT<12 nmol/L and/or cFT<225 pmol/L; n=72). Hypogonadal men were randomly assigned to receive T gel 2% (5 g/daily) or placebo for 6 months. At baseline and follow-up visit (after 6 months), all men filled out the International Prostatic Symptoms Score (IPSS) and NIH-Chronic Prostatitis Symptom Index (NIH-CSPI) questionnaires and underwent a trans-rectal prostate ultrasound. After surgery, prostate tissue was collected.

PD42-09 EFFECTS OF OMEGA-3-RICH FISH OIL (MAG-EPA) ON PROSTATE CANCER: PRELIMINARY RESULTS OF A CLINICAL TRIAL

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy VI1 Apr 2018PD42-09 EFFECTS OF OMEGA-3-RICH FISH OIL (MAG-EPA) ON PROSTATE CANCER: PRELIMINARY RESULTS OF A CLINICAL TRIAL Lisanne Beaudoin, Nikunj Gevariya, Karine Robitaille, Marie-Hélène Guertin, Jean-Francois Pelletier, Pierre Julien, and Vincent Fradet Lisanne BeaudoinLisanne Beaudoin More articles by this author , Nikunj GevariyaNikunj Gevariya More articles by this author , Karine RobitailleKarine Robitaille More articles by this author , Marie-Hélène GuertinMarie-Hélène Guertin More articles by this author , Jean-Francois PelletierJean-Francois Pelletier More articles by this author , Pierre JulienPierre Julien More articles by this author , and Vincent FradetVincent Fradet More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1962AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostate cancer (PCa) is the most common non-skin cancer in North American men. Long chain poly-unsaturated omega-3 (LCn3) fatty acids (FA), mainly eicosapentaenoic acid (EPA), would be beneficial against PCa development and progression likely via anti-inflammatory properties. A phase IIb double-blinded randomized controlled trial is currently ongoing in our research team in order to investigate the effects of an EPA-rich fish oil (MAG-EPA) supplementation on PCa proliferation, as well as on inflammation and quality of life (QoL). In the present study, we aimed to determine the MAG-EPA effects on systemic and prostate tissue inflammation, a secondary outcome of this trial. METHODS 130 patients with a Gleason greater than or equal to 7 PCa treated by radical prostatectomy (RP) were randomized to a daily intake of either MAG-EPA or placebo. The supplementation started 6 weeks before RP for up to one year after surgery. Many medical, clinical and QoL questionnaires as well as biological samples were gathered throughout the study. Without lifting the blind, systemic and local inflammation were assessed by measuring expression levels of 27 inflammatory mediators using the Bio-PlexTM technology. Cytokine levels in plasma and prostate tissue were measured at baseline, RP and 12 months for the first 30 patients who completed the study. RESULTS Preliminary analysis revealed important modulation of circulating levels over time for about half of the patients. Interestingly, we observed two distinct plasmatic cytokine profiles at RP (designated group A and group B). More than half of circulating cytokines were significantly upregulated in group A compared to group B. No significant difference was observed in the prostate tissue between patients at RP. CONCLUSIONS These first preliminary results suggest that systemic inflammation is modulated by the intervention in PCa patients over time. The analysis of the entire cohort is warranted and will likely identify LCn3 modulated cytokines in circulation and in the prostate tissue. This RCT represents a unique setting to study the LCn3 biological effects on PCa. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e817-e818 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Lisanne Beaudoin More articles by this author Nikunj Gevariya More articles by this author Karine Robitaille More articles by this author Marie-Hélène Guertin More articles by this author Jean-Francois Pelletier More articles by this author Pierre Julien More articles by this author Vincent Fradet More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

The influence of endotoxin tolerance on the expression of IL-6 and IL-8 in normal human prostate epithelial cells

Objective Current studies have shown that tissue inflammation plays an important role in the course of development of benign prostate hyperplasia (BPH). Endotoxin tolerance (ET) was found to exist in human tissue cells, such as intestinal epithelial cells and human gingival epithelial cells, and could affect the tissue inflammation and immune responses. Lipopolysaccharide (LPS) generated by G-bacteria such as Escherichia coli, which was considered as the most important pathogen of tissue inflammation of prostate. We intended to analyze the inflammatory cytokines interleukin -6 (IL-6) and interleukin -8 (IL-8) expression of normal human prostate epithelial cells RWPE-1 which were stimulated by LPS repeatedly to find out whether ET exist in human prostate epithelial cells as well. Methods RWPE-1 cells were given stimulation of 1 μg/mL LPS which came from Escherichia coli for 24 hours.After collected the culture supernatant of REWP-1, 1 μg/mL LPS group stimulation was given again to form a model of ET. Expression level of cytokines IL-6 and IL-8 was detected by Millipore human cytokine detection kit instructions, in Luminex platform. Results Expression of IL-6 and IL-8 was significant rising at 6 hours and 12 hours after first LPS stimulation (P<0.05). Compared with first LPS stimulation, expression of IL-6 and IL-8 was significant lower after stimulated by LPS repeatedly (P<0.05). Conclusions Endotoxin tolerance phenomenon exists in normal prostate epithelial cells RWPE-1, and inhibits the expression of IL-6 and IL-8. It may influence the chronic inflammation and immune response of prostate tissue. Key words: Prostate; Endotoxins; Interleukin-6; Interleukin-8

Molecular correlates in urine for the obesity and prostatic inflammation of BPH/LUTS patients

Benign prostatic hyperplasia (BPH) is strongly associated with obesity and prostatic tissue inflammation, but the molecular underpinning of this relationship is not known. Here, we examined the association between urine levels of chemokines/adipokines with histological markers of prostate inflammation, obesity, and lower urinary tract symptoms LUTS in BPH patients. Frozen urine specimens from 207 BPH/LUTS patients enrolled in Nashville Men's Health Study were sent for blinded analysis of 11 analytes, namely sIL-1RA, CXC chemokines (CXCL-1, CXCL-8, CXCL-10), CC chemokines (CCL2, CCL3, CCL5), PDGF-BB, interleukins IL-6, IL-17, and sCD40L using Luminex™ xMAP® technology. After adjusting for age and medication use, the urine levels of analytes were correlated with the scales of obesity, prostate inflammation grade, extent, and markers of lymphocytic infiltration (CD3 and CD20) using linear regression. sIL-1RA levels were significantly raised with higher BMI, waist circumference and waist-hip ratio in BPH patients after correction for multiple testing (P = 0.02). Men with greater overall extent of inflammatory infiltrates and maximal CD3 infiltration were marginally associated with CXCL-10 (P = 0.054) and CCL5 (P = 0.054), respectively. CCL3 in 15 patients with moderate to severe grade inflammation was marginally associated with maximal CD20 infiltration (P = 0.09), whereas CCL3 was undetectable in men with mild prostate tissue inflammation. There was marginal association of sCD40L with AUA-SI scores (P = 0.07). Strong association of sIL-1RA in urine with greater body size supports it as a major molecular correlate of obesity in the urine of BPH patients. Increased urine levels of CXCL-10, CCL5, and CCL3 were marginally associated with the scores for prostate tissue inflammation and lymphocytic infiltration. Overall, elevated urinary chemokines support that BPH is a metabolic disorder and suggest a molecular link between BPH/LUTS and prostatic inflammation.

A Prospective Study of Chronic Inflammation in Benign Prostate Tissue and Risk of Prostate Cancer: Linked PCPT and SELECT Cohorts.

Background: We leveraged two trials to test the hypothesis of an inflammation-prostate cancer link prospectively in men without indication for biopsy.Methods: Prostate Cancer Prevention Trial (PCPT) participants who had an end-of-study biopsy performed per protocol that was negative for cancer and who subsequently enrolled in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) were eligible. We selected all 100 cases and sampled 200 frequency-matched controls and used PCPT end-of-study biopsies as "baseline." Five men with PSA > 4 ng/mL at end-of-study biopsy were excluded. Tissue was located for 92 cases and 193 controls. We visually assessed inflammation in benign tissue. We estimated ORs and 95% confidence intervals (CI) using logistic regression adjusting for age and race.Results: Mean time between biopsy and diagnosis was 5.9 years. In men previously in the PCPT placebo arm, 78.1% of cases (N = 41) and 68.2% of controls (N = 85) had at least one baseline biopsy core (∼5 evaluated per man) with inflammation. The odds of prostate cancer (N = 41 cases) appeared to increase with increasing mean percentage of tissue area with inflammation, a trend that was statistically significant for Gleason sum <4+3 disease (N = 31 cases; vs. 0%, >0-<1.8% OR = 1.70, 1.8-<5.0% OR = 2.39, ≥5% OR = 3.31, Ptrend = 0.047). In men previously in the finasteride arm, prevalence of inflammation did not differ between cases (76.5%; N = 51) and controls (75.0%; N = 108).Conclusions: Benign tissue inflammation was positively associated with prostate cancer.Impact: This first prospective study of men without biopsy indication supports the hypothesis that inflammation influences prostate cancer development. Cancer Epidemiol Biomarkers Prev; 26(10); 1549-57. ©2017 AACR.

Racial differences in prostate inflammation: results from the REDUCE study.

Prostate cancer (PC) risk differs between races, and we previously showed prostate inflammation in benign prostate tissue was linked with a lower future PC risk. However, whether prostate tissue inflammation varies by race is unknown. We analyzed baseline acute and chronic prostate inflammation by race in REDUCE, a 4-year, multicenter, placebo-controlled study where all men had a negative prostate biopsy prior to enrollment. We included 7,982 men with standardized central pathology review to determine the presence or absence of chronic or acute inflammation in baseline prostate biopsy tissue. Logistic regression was used to compare prostate inflammation by race, adjusting for confounders. Of 7,982 men, 7,271 were white (91.1%), 180 (2.3%) black, 131 (1.6%) Asian, 319 (4.0%) Hispanic and 81 (1%) unknown. A total of 78% had chronic and 15% had acute inflammation. On multivariable analysis relative to white men, black men were less likely (OR = 0.65, 95%CI: 0.41-1.03, p = 0.07) and Asian men more likely to have acute inflammation (OR = 1.74, 95%CI: 1.14-2.65, p = 0.001). Hispanic men had similar levels of acute inflammation as white men. Chronic inflammation did not significantly differ across races. We identified racial differences in acute inflammation, particularly in Asian men, in benign prostate tissue that inversely mirrored population-level data on PC race disparity. As we showed in REDUCE that acute inflammation is linked with lower future PC risk, if validated in future studies, these data suggest racial differences in prostatic acute inflammation may contribute in part to race differences in PC risk, especially among Asian men.

Does Inflammation Mediate the Obesity and BPH Relationship? An Epidemiologic Analysis of Body Composition and Inflammatory Markers in Blood, Urine, and Prostate Tissue, and the Relationship with Prostate Enlargement and Lower Urinary Tract Symptoms.

BackgroundBPH is a common disease associated with age and obesity. However, the biological pathways between obesity and BPH are unknown. Our objective was to investigate biomarkers of systemic and prostate tissue inflammation as potential mediators of the obesity and BPH association.MethodsParticipants included 191 men without prostate cancer at prostate biopsy. Trained staff measured weight, height, waist and hip circumferences, and body composition by bioelectric impedance analysis. Systemic inflammation was estimated by serum IL-6, IL-1β, IL-8, and TNF-α; and by urinary prostaglandin E2 metabolite (PGE-M), F2-isoprostane (F2iP), and F2-isoprostane metabolite (F2iP-M) levels. Prostate tissue was scored for grade, aggressiveness, extent, and location of inflammatory regions, and also stained for CD3 and CD20 positive lymphocytes. Analyses investigated the association between multiple body composition scales, systemic inflammation, and prostate tissue inflammation against BPH outcomes, including prostate size at ultrasound and LUTS severity by the AUA-symptom index (AUA-SI).ResultsProstate size was significantly associated with all obesity measures. For example, prostate volume was 5.5 to 9.0 mls larger comparing men in the 25th vs. 75th percentile of % body fat, fat mass (kg) or lean mass (kg). However, prostate size was not associated with proinflammatory cytokines, PGE-M, F2iP, F2iP-M, prostate tissue inflammation scores or immune cell infiltration. In contrast, the severity of prostate tissue inflammation was significantly associated with LUTS, such that there was a 7 point difference in AUA-SI between men with mild vs. severe inflammation (p = 0.004). Additionally, men with a greater waist-hip ratio (WHR) were significantly more likely to have severe prostate tissue inflammation (p = 0.02), and a high WHR was significantly associated with moderate/severe LUTS (OR = 2.56, p = 0.03) among those participants with prostate tissue inflammation.ConclusionThe WHR, an estimate of centralized obesity, was associated with the severity of inflammatory regions in prostate tissue and with LUTS severity among men with inflammation. Our results suggest centralized obesity advances prostate tissue inflammation to increase LUTS severity. Clinically targeting centralized fat deposition may reduce LUTS severity. Mechanistically, the lack of a clear relationship between systemic inflammatory or oxidative stress markers in blood or urine with prostate size or LUTS suggests pathways other than systemic inflammatory signaling may link body adiposity to BPH outcomes.

Inflammation in Benign Prostate Tissue and Prostate Cancer in the Finasteride Arm of the Prostate Cancer Prevention Trial.

A previous analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT) reported 82% overall prevalence of intraprostatic inflammation and identified a link between inflammation and higher-grade prostate cancer and serum PSA. Here, we studied these associations in the PCPT finasteride arm. Prostate cancer cases (N = 197) detected either on a clinically indicated biopsy or on protocol-directed end-of-study biopsy, and frequency-matched controls (N = 248) with no cancer on an end-of-study biopsy were sampled from the finasteride arm. Inflammation in benign prostate tissue was visually assessed using digital images of hematoxylin and eosin-stained sections. Logistic regression was used for statistical analysis. In the finasteride arm, 91.6% of prostate cancer cases and 92.4% of controls had at least one biopsy core with inflammation in benign areas (P < 0.001 for difference compared with placebo arm). Overall, the odds of prostate cancer did not differ by prevalence [OR, 0.90; 95% confidence interval (CI), 0.44-1.84] or extent (P trend = 0.68) of inflammation. Inflammation was not associated with higher-grade disease (prevalence: OR, 1.07; 95% CI, 0.43-2.69). Furthermore, mean PSA concentration did not differ by the prevalence or extent of inflammation in either cases or controls. The prevalence of intraprostatic inflammation was higher in the finasteride than placebo arm of the PCPT, with no association with higher-grade prostate cancer. Finasteride may attenuate the association between inflammation and higher-grade prostate cancer. Moreover, the missing link between intraprostatic inflammation and PSA suggests that finasteride may reduce inflammation-associated PSA elevation.

Investigating the Effects of Regular Resistance Training and Prostatic Massage on Proinflammatory Markers and Serum Prostate-Specific Antigen Levels in Males with Prostate Cancer

Background: Prostate cancer (PC) is one of the most common cancers worldwide. Some studies support that chronic inflammation of prostate tissue plays a role in the development of PC. A variety of growth factors and cytokines may lead to proinflammatory processes within the prostate. Objectives: The aim of the present study was to investigate the effects of eight weeks of regular resistance training and prostatic massage on proinflammatory markers) CRP, IL-6, TNF- α, and IL-10 and serum prostate-specific antigen (PSA levels in males with PC). Patients and Methods: Forty-five patients with PC were selected for this study. They were randomized into either the resistance training intervention group (n = 15), the massage intervention group (n = 15), or the control group (n = 15). Resistance-training patients participated in resistance training for eight weeks, and massage was performed for six weeks on the massage group. Repeated measures analysis of variance (ANOVA) was used to analyze the data (P ≤ 0.05). Results: In the resistance training group, IL-10 levels significantly increased after four (P = 0.055) and eight weeks (P = 0.000). Four and eight weeks of resistance training showed a significant reduction in PSA, CRP, IL-6, and TNF- α levels (P < 0.05). Patients of massage intervention showed an increase in IL-10 after four (P = 0.045) and six weeks (P = 0.005). In addition, four and six weeks of massage intervention showed a significant reduction in PSA, CRP, IL-6, and TNF- α levels (P < 0.05). Conclusions: Regular resistance training and prostatic massage can improve proinflammatory markers and PSA levels in men with PC.