Chronic Prostatitis (Prostate Inflammation) - Causes, Treatment & Symptoms
Received 7 April Published 17 September Volume Pages 75— Review by Single-blind. Peer reviewers approved by Dr Cristina Weinberg. Editor who approved publication: Dr Jan Colli. Gianni Paulis 1,2 1 Andrology Center, Villa Benedetta Clinic, Rome, Italy; 2 Department of Uro-Andrology, Castelfidardo Medical Team, Rome, Italy Abstract: This article focuses on the role that oxidative stress plays in chronic prostatitis, not only with respect to the known impact on symptoms and fertility but also especially in relation to possible prostate cancer development.
If the germ-causing acute prostatitis is not eliminated, the inflammatory process becomes chronic. Confirming the role of oxidative stress in chronic prostatitis, several studies have demonstrated the presence of oxidative stress markers in the genital secretions of patients suffering from the disease. Antioxidants can therefore play an essential role in the treatment of chronic bacterial and non-bacterial prostatitis; in the case of bacterial inflammation, they can be Prostatitis Behandlungstabletten in der Pharmazie with antibiotic therapy.
Moreover, due to their anti-inflammatory properties, antioxidants hinder the progression of inflammation and the possible development of prostate cancer.
Keywords: chronic prostatitis, chronic prostatitis treatment, radical oxygen species, nitrosative stress, antioxidant therapy. Prostatitis is the most common urologic disease in adult males younger than 50 years and the third most frequent urologic diagnosis in men older than 50 years.
The cause of prostatic infection, in most cases, is bacterial, and the most common germs are Gram-negative bacteria, particularly Escherichia coli, Enterobacter, Klebsiella, Serratia, Pseudomonasand Proteus speciesbut Gram-positive bacteria, particularly Enterococcuscan also be responsible for prostatic infection.
Microorganisms responsible for sexually transmitted diseases can also cause prostatic infection; these include Neisseria gonorrhoeaeChlamydia trachomatis, Ureaplasma urealyticum, Mycoplasma Prostatitis Behandlungstabletten in der Pharmazie, Trichomonas vaginalisand Gardnerella vaginalis. High concentrations of free radicals are produced in the tissues during chronic prostatitis, leading to marked tissue damage and DNA fragmentation; excessive epithelial proliferation may then occur, with possible development of prostate cancer.
Our interest in this topic was reinforced by a number of recent studies which, besides pointing to an increase in risk of developing prostate cancer in men with a history of chronic prostatitis, demonstrated that oxidative stress is associated with the development and progression of prostate cancer. This balance is preserved by protective endogenous antioxidant mechanisms.
However, redox homeostasis is altered when there is an excessive production of reactive species, leading to the development of a state of oxidative stress. As a proof of this, several studies have shown that oxidative stress can cause the maintenance and progression of chronic inflammation, contributing to the pathophysiology of many chronic diseases, including chronic prostatitis and prostate cancer. Although in moderate concentrations, reactive species ensure that cell processes run normally, in high concentrations, they cause pathological changes in intracellular substances such as proteins, lipids, and DNA.
When microbial pathogens bacteria, viruses, fungi, etc are detected by pattern recognition receptors PRRsthe immune system produces an acute inflammatory response Figure Prostatitis Behandlungstabletten in der Pharmazie aimed at eradicating the infectious agents.
PRRs are expressed by various innate immunity cells neutrophils, macrophages, monocytes, and dendritic cells and are able to recognize pathogen-associated molecular patterns PAMPsas well as patterns of the external cell walls of bacteria such as the lipopolysaccharides LPSs of Gram-negative bacteria Figure 1 and the lipoteichoic acids and peptidoglycans of Gram-positive bacteria. Figure 1 Schematic illustration of the fundamentals involved in the mechanisms of acute prostatitis.
In particular, MCP-1 acts as a powerful chemotactic agent for circulating monocytes, which turn into macrophages once they have reached the site of inflammation; Prostatitis Behandlungstabletten in der Pharmazie, MCP-1 regulates the recruitment of monocytes and the formation of macrophage infiltrate. MCP-1 is produced by many types of cells, both by natural gene expression and by growth factors, cytokines, and oxidative stress after induction.
During the inflammatory reaction induced by a bacterial infection, a high concentration of inflammatory cells immediately occurs at the infection site; these cells are mainly neutrocytes within and around the prostatic acinifollowed in time by a stromal infiltration formed by lymphocytes and macrophages; in the following days, the neutrocytes gather mainly in the stroma. Production of high amounts of superoxide anion by the inflammatory cells leads to subsequent chemical reactions, with the production of further reactive species such as hydrogen peroxide, hydroxyl radical, hypochlorous acid, and singlet oxygen.
In this phase, the production of ROS, mainly superoxide anion, hydroxyl radical, and hypochlorous acid, is aimed at killing the bacteria responsible for the prostatic infection. SOD is a part of the endogenous antioxidant defenses and intervenes as primary cellular defense against the superoxide anion. Besides neutrocytes and macrophages, lymphocytes are also Prostatitis Behandlungstabletten in der Pharmazie to be present among the cells of the inflammatory infiltrate. Recently, it has been ascertained that some T cells which are part of the adaptive immune system also contribute to acute inflammation.
Furthermore, a downregulation of prostate-specific transcription factor Nkx occurs during bacterial prostatitis. The production of this isoprostane also increases in other conditions associated with oxidative stress smoking, consumption of alcohol, diabetes, aging, etc.
During the acute inflammatory process, inflammatory mediators cytokines, ILs, chemokines, etc are produced in waves, until the stimulus persists, and because they have a short half-life, they are degraded shortly after their release.
Even neutrophils have a short half-life in tissues and die by apoptosis within a few hours. The acute inflammatory process in acute prostatitis ends with the elimination Prostatitis Behandlungstabletten in der Pharmazie the germ. If the germ is not eliminated, the Prostatitis Behandlungstabletten in der Pharmazie process turns chronic Figure 2. Thus, the prostatic inflammation becomes chronic.
Figure 2 Schematic illustration of the fundamentals involved in the mechanisms of chronic prostatitis. More rarely, the inflammatory process can also insidiously present right from the start as a chronic inflammatory response, with no typical manifestation of acute inflammation.
For example, this can occur with prostate tuberculosis and prostatic syphilis. The histopathological profile of chronic prostatitis shows the presence of lymphocyte infiltration, more widely present in the stroma immediately adjacent to the prostatic acini and more scarcely present in the epithelium; macrophages are also present in significant numbers both within the glands and in the intervening stroma.
During inflammation, macrophages can be activated both through the classic pathway M1 macrophages and Prostatitis Behandlungstabletten in der Pharmazie the alternative Prostatitis Behandlungstabletten in der Pharmazie M2 macrophages.
M1 macrophages are inflammatory cells designed to eliminate pathogens and therefore release high amounts of ROS, which Prostatitis Behandlungstabletten in der Pharmazie highly cytotoxic; if the production of ROS is excessive Prostatitis Behandlungstabletten in der Pharmazie uncontrolled, it can cause tissue damage.
Th17 cells, which represent a subgroup of Th cells, produce IL, a cytokine that induces production on the part of macrophages of IL-8 and MCP-1, which have chemotactic effects on white blood cells.
In turn, the activated macrophages stimulate the response of T cells through cytokines such as IL and IL Cellular death and ECM damage result in the release of several molecules originating from the cells cytosolic or nuclear proteins, etc and from ECM degradation. Significant tissue damage is, therefore, a hallmark of chronic inflammation. The high concentration of reactive Prostatitis Behandlungstabletten in der Pharmazie ROS and RNS that occurs during chronic prostatic inflammation is capable of causing direct DNA damage, with consequent sperm DNA fragmentation and its negative effects on fertility.
Inflammation is an immunological response the main purpose of which is to eradicate pathogens and to repair damaged tissues, but if the natural response is not appropriate, excessive tissue repair fibrosis, etc and persistent oxidative stress can maintain and amplify the inflammatory response. Obviously, in the case of bacterial prostatitis, therapy must principally aim at eradication of the germ, with the use of antibiotics that should ideally be able to penetrate into the prostate and reach high tissue concentrations.
Antibiotic therapy should also be associated with anti-inflammatory and antioxidant substances, so as to limit the tissue damage and consequent symptoms as much as possible. In the treatment of chronic prostatitis, several natural substances have been used, but scientific evidence and therapeutic rationale exist for only a few Prostatitis Behandlungstabletten in der Pharmazie them.
Serenoa repens SRor saw palmetto, is very likely the most commonly used plant in the treatment of both prostatitis and benign prostatic hyperplasia.
In a study, Paubert-Braquet et al 75 proved that SR has anti-inflammatory effects as it is able to inhibit the production of 5-lipoxygenase metabolites and leukotrienes. Other studies have found significant positive effects of SR on inflammation biomarkers in biological samples of patients with prostatic inflammation.
Furthermore, several in vitro studies have described the antioxidant and anti-inflammatory activity of most of its components. Currently, available commercial SR extracts contain fatty acids and phytosterols.
Myristic acid SFA is a powerful scavenger of nitric oxide, superoxide, hydroxyl, and lipid peroxide. In particular, linoleic acid also has anti-COX2 anti-inflammatory activity. Previous studies have Prostatitis Behandlungstabletten in der Pharmazie proven that other antioxidant substances are present in SR, including ferulic acid, vanillic acid, triterpenes, gallic acid, caffeic acid esters, flavonoids isoquercetin, avicularin, astragalin, rutin, manghaslin, Prostatitis Behandlungstabletten in der Pharmazie kaempferol.
Quercetin is a flavonoid present in high concentrations in capers, red onion, lovage, and dill. In a randomized, double-blind, placebo-controlled study, Shoskes et al 99 proved that quercetin mg orally twice daily for 4 weeks was able to significantly improve clinical symptoms in patients with chronic prostatitis. Carnitine is a molecule synthesized in Prostatitis Behandlungstabletten in der Pharmazie human body mainly in the liver and kidneys, whereas external natural sources are meat, milk, and codfish.
Carnitine is a very powerful scavenger of superoxide anion, hydrogen peroxide, and peroxynitrite Prostatitis Behandlungstabletten in der Pharmazie also suppresses nitric oxide radical production and iNOS gene expression. Several studies have reported the successful use of pollen extract PE in the treatment of prostatitis. PE is a powerful scavenger of hydroxyl radicals, hydrogen peroxide, and superoxide anion. The main constituents of PE are fatty acids, phenols, and flavonoids.
In particular, linolenic and linoleic acids are present in high amounts, palmitic acid and oleic acid are present in slightly lower quantities; capric acid, eicosenoic acid, and arachidic acid are present in limited quantities; gallic acid and quercetin are also present. A few positive experiences have been reported in the literature on the therapeutic effects of curcumin in chronic prostatitis.
Furthermore, curcumin has been shown to have a chemopreventive effect on the onset of prostate cancer, because it interferes with the proliferation of prostate cancer and the spreading of metastasis through downregulation of androgen receptors ARs and epidermal growth factor receptors EGFRs and promotion of cell cycle arrest. Resveratrol is a natural phenol present in high concentrations in red grapes and grape-derived products eg, red wineblueberries, raspberries, apples, peanuts, plums, mulberry, pine trees Pinus spplegumes Cassia spp, Pterolobium hexapetalumetc.
Monoterpenes are natural essential oils from plants that have antioxidant activities. KG, Bergisch Gladbach, Germany was used to prove their efficacy in the treatment of chronic prostatitis patients. The formula containing the monoterpenes Rowatinex capsules was studied in a randomized controlled trial, and its therapeutic effects on 25 patients suffering from chronic prostatitis were compared with those obtained in another group of 25 patients who were treated with ibuprofen a non-steroidal anti-inflammatory drug.
NIH-CPSI Prostatitis Behandlungstabletten in der Pharmazie a validated questionnaire that is used to assess the intensity of prostatitis symptoms pain, urinary symptoms, and quality of life.
Epilobium is a perennial herbaceous plant that includes various species; the species studied in relation to prostatitis are the following: Epilobium parviflorumEpilobium angustifoliumand Epilobium hirsutum. The properties of Epilobium are due to its high antioxidant content: myricetin, quercetin, and kaempferol flavonoidsand oenothein B a macrocyclic tannin.
In particular, the extract Prostatitis Behandlungstabletten in der Pharmazie Epilobium perviflorum has been shown to have strong antioxidant activity inhibition of enzyme MPOanti-inflammatory activity inhibition of enzymes cyclooxygenase-1 [COX-1] and COX-2and antibacterial activity.
NAC has also been observed in experimental studies that have proven its antioxidant and anti-inflammatory efficacy in prostatitis. Furthermore, NAC has been shown to have chemopreventive activity for prostate cancer, because it strongly suppresses the proliferation, migration, invasion, and adhesion of human prostate cancer cells.
It is evident that oxidative stress plays an important role at various levels in both acute and chronic inflammations. If inflammatory cells were not to release ROS, one of the key elements of the immune Prostatitis Behandlungstabletten in der Pharmazie could not take place, ie, neutralization and killing of the bacteria responsible for the infection. Furthermore, by regulating the functions of T cells, ROS play an important role in the modulation of the immune response.
As chronic prostatitis progresses, fibrotic and calcified areas are inevitably formed, which cause dysuria and reinfections. Confirming the role played by oxidative stress in chronic prostatic inflammation, several studies have proven the presence of oxidative stress markers in genital secretions or urine of patients suffering from the disease.
To date, a very few studies have analyzed the therapeutic effect of antioxidants in chronic prostatitis patients, although numerous studies have demonstrated Prostatitis Behandlungstabletten in der Pharmazie properties of the various antioxidants and pointed out their potential efficacy. Further randomized controlled studies on this topic are therefore needed, especially considering the enormous growth in interest in chronic prostatitis over the past few years, since excessive oxidative stress can favor the progression of inflammation and the development of prostate cancer.
How common is prostatitis? A national survey of physician visits. J Urol. Epidemiology of prostatitis. Int J Antimicrob Agents. X Chromosomal short tandem repeat polymorphisms near the phosphoglycerate kinase gene in men with chronic prostatitis. Biochim Biophys Acta. Dohle GR. Inflammatory-associated obstructions of the male reproductive tract.