IL-17 Exacerbates Experimental Autoimmune Prostatitis via CXCL1/CXCL2-Mediated Neutrophil Infiltration

Author(s):  
Cheng Zhang ◽  
Jia Chen ◽  
Hui Wang ◽  
Jing Chen ◽  
Mei-Juan Zheng ◽  
...  

Abstract Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a poorly understood disease. Accumulating evidence suggests that autoimmune dysfunction is involved in the development of CP/CPPS. IL-17 is associated with the occurrence and development of several chronic autoimmune inflammatory diseases. However, the molecular mechanisms underlying the role of IL-17 in CP/CPPS remain unclear. Herein, we first confirmed that IL-17 was increased in the prostate tissues of experimental autoimmune prostatitis (EAP) mice. Corresponding to the increase of IL-17 in the prostate of EAP, neutrophil infiltration and the levels of CXCL1 and CXCL2 (CXC chemokine ligands 1 and 2) were also increased. Treatment of EAP mice with IL-17-neutralizing monoclonal antibody (mAb) resulted in a decreased number of infiltrated neutrophils, as well as the CXCL1 and CXCL2 level. Depletion of neutrophil by anti-Ly6G antibodies ameliorated inflammatory changes and hyperalgesia caused by EAP. Fucoidan, which could potently inhibit neutrophil migration, could also ameliorate the manifestations of EAP. Our finding suggested that IL-17 promoted the production of CXCL1 and CXCL2, which subsequently triggered neutrophil chemotaxis to prostate tissues. And fucoidan might be a potential drug for the therapy of EAP by the effectively inhibiting on neutrophil infiltration.

2019 ◽  
Vol 6 (4) ◽  
pp. 27-35
Author(s):  
V. A. Kruglov ◽  
F. R. Asfandiyarov ◽  
S. N. Vybornov ◽  
K. S. Seyidov

Introduction. Chronic pelvic pain syndrome is an urgent and widely discussed problem in the medical community. Despite the efforts made by a wide range of specialists, there is currently no universally accepted universal approach to the diagnosis and treatment of this condition. The article provides a description and results of applying its own approach to the management of patients with chronic pelvic pain syndrome.Purpose of research. The aim of the work was to improve the practical results of treatment of patients suffering from chronic pelvic pain syndrome.Materials and methods. The results of the examination and treatment of 46 men aged from 26 to 57 years are presented. The leading complaint of the patients was the long-term pain in the pelvic and / or perineal region. According to the survey results, 43.5% of patients showed signs of inflammation in the prostate gland, 56.5% showed no symptoms. Patients with proven inflammatory changes in the prostate gland were divided into two groups: the first group received the “standard” therapy of chronic prostatitis (antibiotics, prostate-tropic drugs, microcirculation and immunocorrection enhancers, physiotherapy), in the second group the patients received the “standard” treatment in combination with myofascial blockades and neuropathic pain therapy. Patients without inflammatory changes in the prostate were combined into a third group and received only myofascial blockade and neuropathic pain therapy.Results. Pain in chronic pelvic pain syndrome is most often localized in the perineal region and in the inguinal zones, while the presence or absence of a proven inflammatory component in the prostate gland does not significantly affect the localization and degree of pain, nor the assessment of quality of life. The pelvic myofascial syndromes are detected in the majority of patients with CPPS and their targeted correction in the framework of complex therapy has a positive effect on the results of patient treatment.Conclusions. Correction of musculo-tonic disorders in chronic pelvic pain syndrome was accompanied by a statistically significant reduction in pain on a 10-point numerical rating scale for pain, a decrease in the I-PSS index.


2020 ◽  
pp. 162-164
Author(s):  
І.V. Lakhno

Background. Pelvic inflammatory diseases (PID) occur in 12-13 % of young women, 65-70 % of outpatients and 30 % of inpatients with gynecological diseases. The consequences of PID include infertility, chronic pelvic pain syndrome, menstrual disorders, etc. Treatment of PID is a multidisciplinary problem in the field of gynecology, urology, and venereology. Objective. To describe the modern treatment of PID. Materials and methods. Analysis of literature sources on this issue; own study to study the effectiveness of the PID treatment with Reosorbilact (“Yuria-Pharm”) and levofloxacin + ornidazole (Grandazole, “Yuria-Pharm”). Women of the main group were additionally prescribed fluconazole, diclofenac, vaginal baths with Dekasan (“Yuria-Pharm”). The treatment lasted 7 days. Treatment of the comparison group included ceftriaxone, metronidazole, diclofenac, doxycycline, fluconazole, chlorhexidine. Results and discussion. Chronic PID often have a latent course. 70 % of them are caused by the specific flora (Chlamydia trachomatis, Neisseria gonorrheae, anaerobes, gram-negative bacteria). The frequency of mixed polymicrobial processes and polychemical resistance is increasing. The presence of bacterial vaginosis allows the infections to recur constantly. Pathogens that cause PID can also cause extragenital pathological conditions (perihepatitis, Reiter’s syndrome, enteritis, colitis, cholecystitis). Diagnostic criteria for PID are the following: pain in the appendages or when the cervix is displaced during the bimanual examination, fever, leukorrhea and menorrhagia. If PID is suspected, a bimanual examination should be performed to rule out acute appendicitis. Ultrasound or computed tomography should be performed to rule out tuboovarian tumors and make a differential diagnosis with intestinal or urinary tract disease. The etiological diagnosis requires microbial and molecular examination of the contents of the vagina and cervix. Fluoroquinolones with metronidazole for 14 days are the first line therapy of uncomplicated PID. Chronic inflammation has no mechanisms of self-completion and can last for years and decades. In gynecology, chronic inflammation is divided into infectious, allergic and autoimmune type. Patients with recurrence of chronic PID are characterized by mixed infections and the formation of biofilms, allergies, low efficiency of immune cells. To overcome the polychemical resistance of pathogens, it is advisable to use effective hydrodynamic drugs that can act as a hydraulic conductor of the antibacterial agent, improve microcirculation in the inflammatory focus, optimize venous hemodynamics and lymphatic drainage. Sorbitol has all these properties. In addition, sorbitol increases the tropism of fluoroquinolones to gram-positive microorganisms and has own bacteriostatic effect. In the own study, it was found that the increase in the resistance index of the ovarian arteries was associated with increased intensity of pain in the lower abdomen, pathological vaginal discharge and fever, which justifies the use of vasoactive drugs in the treatment of PID. In the Reosorbilact and Grandazole treatment groups, normalization of clinical and laboratory parameters occurred in 100 % of women, whereas in 12.1 % of control group members the result was considered insufficient, requiring antibiotic replacement and continuation of therapy. Conclusions. 1. In women with PID, there is a connection between blood flow in the ovarian arteries and the severity of the clinical signs of PID, which justifies the use of hemodynamic drugs. 2. Improvement of intrapelvic hemodynamics on the background of Reosorbilact was the key to successful use of Grandazole. 3. Co-administration of Reosorbilact and Grandazole is a promising method of empirical therapy of PID.


2008 ◽  
Vol 294 (4) ◽  
pp. R1268-R1275 ◽  
Author(s):  
Charles N. Rudick ◽  
Anthony J. Schaeffer ◽  
Praveen Thumbikat

Pain is the hallmark of patients with chronic prostatitis (CP) and chronic pelvic pain syndrome (CPPS). Despite numerous hypotheses, the etiology and pathogenesis remain unknown. To better understand CP/CPPS, we used a murine experimental autoimmune prostatitis model to examine the development, localization, and modulation of pelvic pain. Pelvic pain was detected 5 days after antigen instillation and was sustained beyond 30 days, indicating the development of chronic pain. The pain was attenuated by lidocaine treatment into the prostate, but not into the bladder or the colon, suggesting that pain originated from the prostate. Experimental autoimmune prostatitis histopathology was confined to the prostate with focal periglandular inflammatory infiltrates in the ventral, dorsolateral, and anterior lobes of the mouse prostate. Inflammation and pelvic pain were positively correlated and increased with time. Morphologically, the dorsolateral prostate alone showed significantly increased neuronal fiber distribution, as evidenced by increased protein gene product 9.5 expression. Pelvic pain was attenuated by treatment with the neuromodulator gabapentin, suggesting spinal and/or supraspinal contribution to chronic pain. These results provide the basis for identifying mechanisms that regulate pelvic pain and the testing of therapeutic agents that block pain development in CP/CPPS.


Pain ◽  
2014 ◽  
Vol 155 (7) ◽  
pp. 1328-1338 ◽  
Author(s):  
Kenny Roman ◽  
Joseph D. Done ◽  
Anthony J. Schaeffer ◽  
Stephen F. Murphy ◽  
Praveen Thumbikat

2020 ◽  
pp. 66-68
Author(s):  
О.V. Hryshchenko

Background. Over the last decade, women in many countries around the world have seen an increase in the number of urogenital infections, which occupy the first place in the structure of obstetric and gynecological morbidity. Risk factors for the development of inflammatory diseases include the invasive procedures and irrigations, sexual activity, unreasonable treatment, refusal to restore eubiosis after antimicrobial and antifungal therapy, the presence of intrauterine devices, etc. Objective. To characterize the influence of the spread of antibiotic-resistant pathogens on the course of gynecological diseases. Materials and methods. Analysis of literature data on this issue. Results and discussion. Peculiarities of the vaginal infections course’ nowadays include prevalence of self-treatment, uncontrolled antibiotics (AB) use, the development of AB resistance, and the presence of extragenital pathology. Pelvic inflammatory disease (PID) comprise 75 % of all gynecological diseases. PID cause such complications as chronic pelvic pain syndrome, purulent tubo-ovarian tumors, cervical neoplasia, and infertility. The risk of the latter increases depending on the number of episodes of PID. Principles of PID treatment include comprehensiveness, etiopathogenetic orientation, individualization and recurrence prevention. Antibacterial therapy (ABT), nonsteroidal anti-inflammatory drugs, infusions, transfusions, detoxification therapy, medications aimed at the improvement of hemodynamics and microcirculation, immunotherapy, and topical therapy are used in the treatment of PID. The consequences of irrational ABT include an increase in the resistance of pathogenic flora, disruption of the normal body biocenosis, increased risk of adverse reactions, impaired immune function and increased treatment costs. Macrolides, cephalosporins, fluoroquinolones and aminoglycosides are the main groups of AB used for the systemic ABT in PID. Tobramycin (one of the latter group) is active against 83.4 % of pathogens that cause urogenital infections. Other advantages of tobramycin include synergism with β-lactams and high activity against Pseudomonas aeruginosa – a bacterium with a high and dangerous potential for AB resistance. In turn, fluoroquinolones are active against 94 % of pathogens that cause urogenital infections; they are able to penetrate cell membranes and have a low potential for the formation of AB resistance. The combination of fluoroquinolone levofloxacin with ornidazole (Grandazole, “Yuria-Pharm”) can improve the general condition and reduce pain on the 3rd day of treatment of PID, normalize the temperature, reduce hospital stay. Co-administration of levofloxacin and ornidazole as part of an infusion solution is more rational than their separate use. Such treatment minimizes the risk of allergic reactions and side effects. For local sanitation of vagina and vulva, it is advisable to use decamethoxine (Dekasan, “Yuria-Pharm”) – a basic antiseptic that acts on various types of bacteria, viruses, fungi and protozoa. Additional benefits are anti-inflammatory, desensitizing and antispasmodic action. Decamethoxine also effectively reduces the adhesion of staphylococci and Escherichia coli. One of the main advantages of decamethoxine is the lack of effect on human cells. Conclusions. 1. PID are the most common diseases in the field of obstetrics and gynecology. 2. Care should be taken when choosing a drug for ABT. 3. The combination of levofloxacin and ornidazole can effectively treat PID, reducing the duration of inpatient treatment. 4. For local sanitation of the vagina and vulva, it is advisable to use decamethoxine.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoliang Hua ◽  
Shengdong Ge ◽  
Meng Zhang ◽  
Fan Mo ◽  
Ligang Zhang ◽  
...  

Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) is an inflammatory immune disease characterized by intraprostatic leukocyte infiltration and pelvic or perineal pain. Macrophages play vital roles in the pathogenesis of CP/CPPS. However, the mechanisms controlling the activation and chemotaxis of macrophages in CP/CPPS remain unclear. This study aimed to investigate the roles of the CXCL10/CXCR3 pathway in the activation and chemotaxis of macrophages in CP/CPPS patients. The serums of CP/CPPS patients and healthy volunteers were collected and measured. Results showed that CXCL10 expression was significantly elevated and correlated with the severity of CP/CPPS patients. The experimental autoimmune prostatitis (EAP) model was generated, and adeno-associated virus and CXCR3 inhibitors were used to treat EAP mice. Immunofluorescence, flow cytometry, and Western blotting were used to analyze the functional phenotype and regulation mechanism of macrophages. Results showed that CXCL10 deficiency ameliorates EAP severity by inhibiting infiltration of macrophages to prostate. Moreover, CXCL10 could induce macrophage migrations and secretions of proinflammatory mediators via CXCR3, which consequently activated the downstream Erk1/2 and p38 MAPK signaling pathways. We also showed that prostatic stromal cell is a potential source of CXCL10. Our results indicated CXCL10 as an important mediator involved in inflammatory infiltration and pain symptoms of prostatitis by promoting the migration of macrophages and secretion of inflammatory mediators via CXCR3-mediated ERK and p38 MAPK activation.


2012 ◽  
Vol 303 (6) ◽  
pp. R580-R589 ◽  
Author(s):  
Marsha L. Quick ◽  
Soumi Mukherjee ◽  
Charles N. Rudick ◽  
Joseph D. Done ◽  
Anthony J. Schaeffer ◽  
...  

Experimental autoimmune prostatitis (EAP) is a murine model of chronic prostatitis/chronic pelvic pain syndrome (CPPS) in men, a syndrome characterized by chronic pelvic pain. We have demonstrated that chemokine ligands CCL2 and CCL3 are biomarkers that correlate with pelvic pain symptoms. We postulated that CCL2 and CCL3 play a functional role in CPPS and therefore examined their expression in EAP. Upon examination of the prostate 5 days after induction of EAP, CCL2 mRNA was elevated 2- to 3-fold, CCL8 by 15-fold, CCL12 by 12- to 13-fold, and CXCL9 by 2- to 4-fold compared with control mice. At 10 days the major chemokines were CXCL13 and CXCL2; at 20 days CCL2 (1- to 2-fold), CCL3 (2- to 3-fold) and CCL11 (2- to 3-fold); and at 30 days, CCL12 (20- to 35-fold) and smaller increases in CCL2, CCL3, and XCL1. Chemokine elevations were accompanied by increases in mast cells and B cells at 5 days, monocytes and neutrophils at day 10, CD4+ T cells at day 20, and CD4+ and CD8+ T cells at day 30. Anti-CCL2 and anti-CCL3 neutralizing antibodies administered at EAP onset attenuated pelvic pain development, but only anti-CCL2 antibodies were effective therapeutically. CCL2- and its cognate receptor CCR2-deficient mice were completely protected from development of pain symptoms but assumed susceptibility after reconstitution with wild-type bone marrow. CCL3-deficient mice showed resistance to the maintenance of pelvic pain while CCR5-deficient mice did not show any lessening of pelvic pain severity. These results suggest that the CCL2-CCR2 axis and CCL3 are important mediators of chronic pelvic pain in EAP.


2018 ◽  
Vol 73 (4) ◽  
pp. 221-228
Author(s):  
Daria E. Nikiforova ◽  
Tatyana A. Makarenko ◽  
Alla B. Salmina

This article systematizes the results of studies on the pathogenetic mechanisms of CPPS formation in patients with EGE. Pain is one of the severe clinical manifestations and complications of endometriosis. To ease the pain in patients with EGE is complex but urgent task. Long diagnostic search (mean period 5−8 years) leads to the formation of a persistent Autonomous pain syndrome associated with relapses of pain even after a com-prehensive treatment of patients (surgical and/or long-term hormonal). Patients with endometriosis suffer from mixed pain including neuropathic and nociceptive components which is proved by the example of expression in ectopic foci of specific biomarkers. Therefore, the question of early non-invasive diagnosis of endometriosis is very vital and can be solved by the development of a diagnostic panel consisting of biomarkers expressed by ectopic foci at the initial stage of the disease.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Carlos Pérez-Alvarado ◽  
Consuelo Gómez ◽  
Miguel Reyes ◽  
Mario García ◽  
Elizabeth Pérez ◽  
...  

Objective.To evaluate the anti-inflammatory properties of Dialyzable Leukocyte Extract (DLE) in a murine model of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).Methods.Histopathological characterization, prostatein Enzyme-Linked Immunosorbent Assay, and immunohistochemical analysis for CD45, TNF-α, IFN-γ, IL-6, IL-17, and IL-4 molecules were done in prostatic Wistar rats treated with DLE, placebo, or Dexamethasone.Results.Histopathological analysis of animals induced to prostatitis showed inflammatory infiltrate, mainly constituted by leucocytes and mast cells as well as Benign Prostatic Hyperplasia. Serum prostatein concentrations were 14 times higher than those displayed by healthy animals. After DLE and Dexamethasone treatments, the inflammatory infiltrate decreased; the tissue morphology was similar to that of a normal prostate, and the prostatein decreased to the basal levels of healthy animals. DLE treatment produced a decreased expression of the cell surface marker CD45 and the proinflammatory cytokines TNF-α, IFN-γ, IL-6, and IL-17. On the other hand, the expression of anti-inflammatory cytokine IL-4 increased in both the Dexamethasone and DLE groups.Conclusion.DLE is able to modulate the inflammatory response in Experimental Autoimmune Prostatitis (EAP).


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