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Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), also known as National Institutes of Health (NIH) type III prostatitis, is a common disorder with an unclear etiology and no known curative treatments. Based on the presence or absence of leukocytes in expressed prostatic secretion (EPS), CP/CPPS is classified further into IIIa (inflammatory) and IIIb (noninflammatory) subtypes. However, the severity of symptoms is not entirely consistent with the white blood cell (WBC) count. Following the preliminary finding of a link between inflammatory cytokines and CP/CPPS, we performed this clinical study with the aim of identifying cytokines that are differentially expressed according to whether the prostatitis subtype is IIIa or IIIb. We found that granulocyte colony-stimulating factor (G-CSF), interleukin-18 (IL-18), and monocyte chemoattractant protein-1 (MCP-1) levels were significantly elevated and interferon-inducible protein-10 (IP-10) and platelet-derived growth factor-BB (PDGF-BB) levels were downregulated in the EPS of patients with type IIIa prostatitis. In a word, it is a meaningful study in which we investigate the levels of various cytokines in EPS according to whether prostatitis is the IIIa or IIIb subtype. The combination of G-CSF, IL-18, MCP-1, IP-10, and PDGF-BB expression levels could form a basis for classification, diagnosis, and therapeutic targets in clinical CP/CPPS.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a urinary disorder that affects youthful to middle-aged men most frequently. It has been revealed that Th17/Treg imbalance is a crucial factor in the pathophysiological mechanisms behind this disease. However, this imbalance’s mechanisms are unknown. In the experimental autoimmune prostatitis (EAP) mouse model, the NLRP3 inflammasome was turned on, IL-1β levels went up. Moreover, there exists a discernible positive association between the upsurge in IL-1β and the perturbation of Th17/Treg equilibrium. Additionally, we have revealed that IL-1β plays a vital role in promoting the differentiation of Naïve CD4+ T cells into the Th17 cells and enhances the conversion of Treg cells into Th17 cells. Further studies revealed that IL-1β promotes STAT3 phosphorylation, which is what causes Treg cells to become Th17 cells. All data strongly suggest that the NLRP3 inflammatory influence Th17 cell development and the conversion of Treg cells into Th17 cells through IL-1β, disrupting the Th17/Treg balance and exacerbating EAP inflammation. In this article, we provide new theories for the pathogenesis of CP/CPPS and propose new prevention and therapy methods.

Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common disorder associated with voiding symptoms and pain in the pelvic or perineal area. Macrophages, particularly the pro-inflammatory M1 subtype, are crucial initiating of CP/CPPS. Interferon regulatory factor 7 (Irf7) has been implicated in promoting M1 polarization, contributing to the onset and progression of autoimmunity. However, the role of Irf7 in the etiology and progression of CP/CPPS remains unclear. Method We established the experimental autoimmune prostatitis (EAP) mouse model by subcutaneous injection of prostate antigen combined with complete Freund’s adjuvant. Six weeks after the first immunization, we analyzed the prostates, spleen, and blood to assess the degree of prostate inflammation, Irf7 expression levels, glycolysis, and M1 polarization to evaluate whether Irf7 could exacerbate the development of EAP by enhancing Hif-1α transcription, thereby increasing glycolysis and M1 polarization. Further investigations included sh-Irf7 intervention, Dimethyloxalylglycine (a Hif-1α agonist), and in vitro M1 polarization experiments. We also employed ChIP assays, dual-luciferase reporter assays, and q-PCR to explore if Irf7 could directly interact with the Hif-1α promoter in macrophages. Results In the EAP mouse and cell models, elevated Irf7 expression was observed in inflamed tissues and cells. Reducing Irf7 expression decreased M1 cell glycolysis by inhibiting the nuclear translocation of Hif-1α, thus mitigating M1 cell polarization. Additionally, Irf7 was identified as a transcription factor that regulates Hif-1α transcription by interacting with its promoter in macrophages, confirmed through ChIP and dual-luciferase assays. Co-culturing macrophage cells with 3T3 fibroblasts with reduced Irf7 levels resulted in decreased fibrosis, and a significant reduction in prostate tissue fibrosis was noted in mice with Irf7 knockdown. Conclusion Our findings indicate that Irf7 can contribute to the development and progression of CP/CPPS by promoting glycolysis, which can enhance both M1 polarization as well as interstitial fibrosis in the prostate. This process was found to be mediated by the upregulation of Hif-1α transcription, presenting new potential therapeutic targets for managing CP/CPPS.

Definitive diagnosis and selection of effective treatment for chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are frustrations encountered frequently by urology care providers in their practice. Knowledge of etiology and pathophysiology is not sufficient and therapeutic guidelines have not yielded acceptable outcomes and prognoses for both patients and care providers. The authors present updated perspectives on CP/CPPS, including definition, diagnosis, treatment, and prognosis, based on literature review and clinical experience. A key point is to shift the diagnostic and therapeutic focus from a single entity of disease toward associated symptoms of CP/CPPS. An individualized multimodal treatment approach to cope with the course of the disorder is proposed. Communications and personal/family/community supports are emphasized as an important component in the therapeutic regime and rehabilitation of patients with CP/CPPS. The purpose is to improve comprehension on CP/CPPS and to help care providers and patients to achieve the goal of medical intervention—relieving associated symptoms of CP/CPPS and improving the quality of life.

Cumulative evidence suggests that abnormal differentiation of T lymphocytes influences the pathogenesis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Thus, understanding the immune activation landscape of CP/CPPS would be helpful for improving therapeutic strategies. Here, we utilized BD™ AbSeq to digitally quantify both the protein and mRNA expression levels in single peripheral blood T cells from two CP/CPPS patients and two healthy controls. We utilized an integrated strategy based on canonical correlation analysis of 10 000+ AbSeq profiles and identified fifteen unique T‐cell subpopulations. Notably, we found that the proportion of cluster 0 in the CP/CPPS group (30.35%) was significantly increased compared with the proportion in the healthy control group (9.38%); cluster 0 was defined as effector T cells based on differentially expressed genes/proteins. Flow cytometry assays confirmed that the proportions of effector T‐cell subpopulations, particularly central memory T cells, T helper (Th)1, Th17 and Th22 cells, in the peripheral blood mononuclear cell populations of patients with CP/CPPS were significantly increased compared with those of healthy controls (P < 0.05), further confirming that aberration of effector T cells possibly leads to or intensifies CP/CPPS. Our results provide novel insights into the underlying mechanisms of CP/CPPS, which will be beneficial for its treatment.

This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on erectile function in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). A retrospective study was conducted on 657 CP/CPPS patients who visited The Third Xiangya Hospital of Central South University (Changsha, China) from November 2018 to November 2022. Patients were divided into two groups based on the timeline before and after the COVID-19 outbreak in China. The severity of CP/CPPS, penile erection status, anxiety, and depression was evaluated using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), International Index of Erectile Function-5 (IIEF-5), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scales, respectively. Compared with patients before the COVID-19 outbreak, more CP/CPPS patients developed severe erectile dysfunction (ED) due to depression and anxiety caused by the pandemic. After developing moderate-to-severe ED, mild and moderate-to-severe CP/CPPS patients exhibited more apparent symptoms of anxiety and depression (P < 0.001 and P = 0.001, respectively), forming a vicious cycle. The COVID-19 pandemic has adversely affected the psychological status of CP/CPPS patients, exacerbating their clinical symptoms and complicating ED. The exacerbation of clinical symptoms further worsens the anxiety and depression status of patients, forming a vicious cycle. During the COVID-19 pandemic, paying more attention to the mental health of CP/CPPS patients, strengthening psychological interventions, and achieving better treatment outcomes are necessary.

Background Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a debilitating condition affecting 2–10% of men globally. Its symptoms, including pelvic pain, urinary problems, and reduced quality of life, vary widely. Despite extensive research, a definitive treatment remains elusive. Alpha-adrenergic antagonists are frequently used to manage urinary symptoms, while analgesics are employed for pain. However, the long-term efficacy of alpha-adrenergic antagonists for pelvic pain requires further investigation. CP/CPPS places a significant burden on healthcare systems and the economy. This systematic review aims to evaluate the effectiveness of alpha-adrenergic antagonists in reducing pain symptoms in men with CP/CPPS compared to placebo. Methods A systematic search of randomized, placebo-controlled trials evaluating the effectiveness of alpha-adrenergic antagonists for the treatment of pain in CP/CPPS was conducted and captured all available studies (n = 680). After application of exclusion criteria, five studies were identified as suitable for inclusion. Results Four papers consisting of five studies, containing a total of 578 participants, were evaluated. The combined effects found no difference in pain relief between treated and control subjects for the data from the five studies in the meta-analysis ( P  = 0.106), with the 95% CI for the random effects model containing a value of 0.00. Conclusion In adults with CP/CPPS, alpha-adrenergic antagonists were ineffective as monotherapy to treat pain. Further studies are needed to address possible confounding variables for alpha-adrenergic antagonist efficacy. These findings suggest that alpha-adrenergic antagonists as monotherapy are not effective for pain reduction in CP/CPPS and highlight the need for further research to explore combination therapies or other treatment modalities.

Purpose Acupuncture has been recommended as an effective therapy to improve symptoms of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). We conducted this secondary analysis to explore the factors that may influence the response of patients with CP/CPPS to acupuncture. Methods This secondary analysis was based on a randomized controlled trial demonstrating the efficacy of acupuncture among patients with CP/CPPS. Responder is defined as a patient with a decrease of  ≥ 6 points in National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) total score from baseline at the 32 week. 206 patients who received acupuncture treatment and completed 32-week follow-up were included in this secondary analysis. Descriptive statistics were used to describe the demographic and clinical characteristics of both responders and non-responders in acupuncture group. Logistic regression analysis with bootstrapping was made to identify potential factors that contributed to the effectiveness of acupuncture for treating CP/CPPS. Responders and non-responders were listed as dependent variables. Results In this study, 130 (63.11%) patients were assessed as responders. The results showed that men with non-sedentariness (OR 4.170 [95%CI 1.837 to 9.463; P  = 0.001]), non-smoking habit (OR 2.824 [95%CI 1.453 to 5.487; P  = 0.002]), without comorbidity (OR 8.788 [95%CI 1.912 to 40.295; P  = 0.005]), and severe NIH-CPSI total score (OR 0.227 [95%CI 0.114 to 0.450; P  < 0.0001]) benefited more from acupuncture intervention. Conclusion CP/CPPS patients who are active, non-smokers, without comorbidity, and had severe symptoms may be more likely to respond to acupuncture.

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is the most common urologic morbidity in men younger than 50 years and is characterized by a diverse range of pain and inflammatory symptoms, both in type and severity, that involve the region of the pelvis, perineum, scrotum, rectum, testes, penis, and lower back. In most patients, pain is accompanied by inflammation in the absence of an invading infectious agent. Since CP/CPPS etiology is still not well established, available therapeutic options for patients are far from satisfactory for either physicians or patients. During the past two decades, chronic inflammation has been deeply explored as the cause of CP/CPPS. In this review article, we summarize the current knowledge regarding immunological mechanisms underlying chronic pelvic pain and prostate inflammation in CP/CPPS. Cumulative evidence obtained from both human disease and animal models indicate that several factors may trigger chronic inflammation in the form of autoimmunity against prostate, fostering chronic prostate recruitment of Th1 cells, and different other leukocytes, including mast cells, which might be the main actors in the consequent development of chronic pelvic pain. Thus, the local inflammatory milieu and the secretion of inflammatory mediators may induce neural sensitization leading to chronic pelvic pain development. Although scientific advances are encouraging, additional studies are urgently needed to establish the relationship between prostatitis development, mast cell recruitment to the prostate, and the precise mechanisms by which they would induce pelvic pain.

PurposeTo investigate the difference in gut microbiome composition between patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and healthy controls, and to assess the potential of gut microbiota as predictive markers for CP/CPPS risk.MethodsThe present study included 41 CP/CPPS patients and 43 healthy controls in China. Fecal specimen data were obtained and analysed using 16S rRNA gene sequencing. Alpha and beta-diversity indices, relative microbiome abundances, cluster analysis, and linear discriminant analysis effect size (LEfSe) were employed. Microbial biomarkers were selected for the development of a diagnostic classification model, and the functional prediction was conducted using PICRUSt2.ResultsAlpha-diversity measures revealed no statistically significant difference in bacterial community structure between CP/CPPS patients and controls. However, significant differences were observed in the relative abundances of several bacterial genera. Beta-diversity analysis revealed a distinct separation between the two groups. Significant inter-group differences were noted at various taxonomic levels, with specific bacterial genera being significantly different in abundance. The LEfSe analysis indicated that three bacterial species were highly representative and seven bacterial species were low in CP/CPPS patients as compared to the control group. A diagnostic model for CP/CPPS based on microbial biomarkers exhibited good performance. PICRUSt2 functional profiling indicated significant differences in the development and regeneration pathway.ConclusionSignificant differences in the gut microbiome composition were found between groups. The study provided a novel diagnostic model for CP/CPPS based on microbiota, presenting promising potential for future therapeutic targets and non-invasive diagnostic biomarkers for CP/CPPS patients.