Clinicopathophysiological Analysis of Immune Disorders in Patients with Chronic Prostatitis

The dissertation is devoted to a clinicopathophysiological analysis of immune disorders in patients with chronic prostatitis, encompassing bacterial and abacterial forms of the disease. The research is aimed at studying the features of functional-metabolic and immunological disturbances in the body of patients with chronic prostatitis, as well as evaluating the efficacy of immunomodulatory therapy using glucosaminylmuramyl dipeptide (lycopide) as part of comprehensive treatment. Patient examination was conducted to identify changes in cellular and humoral components of immunity, phagocytic activity of leukocytes, intensity of free radical oxidation processes, and the state of mucosa-associated immunity. The obtained data make it possible to establish the role of immune disorders in the pathogenesis of chronic prostatitis and to substantiate the application of immunocorrective therapy.

Relevance of the Problem. Chronic prostatitis is one of the most prevalent, difficult to diagnose and treat diseases in urological practice [44, 71, 188]. It affects men of all ages and ethnic groups [157, 170, 190, 210], being the most common disease in men under 50 years of age and the third most frequent urological diagnosis in men over 50 years (after adenoma and prostate cancer). The relevance of the problem of chronic prostatitis is associated with its high prevalence [133, 190], stubborn course, unsatisfactory treatment outcomes [149], and frequent relapses [197].

The high social significance of the disease is due to its predominant affectation of individuals of young age (from 20 to 45 years), its negative impact on sexual, reproductive functions, and the psychoemotional sphere, and a significant deterioration in the quality of life of men, which is comparable to the condition of patients who have suffered acute myocardial infarction, suffer from Crohn's disease, heart failure, or diabetes mellitus [86, 202].

At present, the existence of bacterial and abacterial chronic prostatitis is recognized by most authors [94].

Modern medicine does not possess in-depth and reliable information on the causes and mechanisms of development of chronic prostatitis, particularly abacterial prostatitis [69, 72, 75].

At the current stage, immunological disturbances in chronic prostatitis are regarded as an important component in the pathogenesis of bacterial and, especially, abacterial chronic prostatitis. Beginning as an infectious-inflammatory process, prostatitis subsequently acquires a stubborn course due to the formation of immunological disturbances, ultimately leading to autoimmune pathology [137]. The reality of autoaggression is confirmed by the detection of circulating antibodies to prostate tissue [132] and the deposition of circulating immune complexes in the affected tissue [30, 150].

In chronic prostatitis, changes occur in local and systemic immunity, including both cellular and humoral components and factors of nonspecific defense, often resulting in a secondary immunodeficient state [19, 69].

Chronic prostatitis is characterized by resistance to the administered therapy, as the etiology and pathogenesis of the disease remain unknown in most cases, and as a consequence, treatment is empirical and often ineffective [142]. Despite a wide range of pharmacological therapy methods, physiotherapeutic interventions, and sanatorium-resort treatment, a sustained positive effect is not always achievable. Therefore, the development of new diagnostic and treatment methods remains a relevant problem of modern urology [120]. The insufficient study of immunological changes, as well as the absence of their correction in complex therapy of chronic prostatitis, remains an unresolved problem [31].

Taking the above into account, the study of the immune system in patients with chronic prostatitis using highly sensitive laboratory research methods appears to be of paramount importance, as it will clarify the understanding of the pathogenesis of bacterial and abacterial prostatitis, since the aforementioned aspects have not received adequate coverage in the modern literature.

Objective of the Research.

Based on the study of leading pathogenetic factors of the recurrent course of chronic bacterial and abacterial prostatitis, to evaluate the efficacy of the use of the immunomodulator glucosaminylmuramyl dipeptide (lycopide) in complex therapy of this category of patients.

Tasks of the Research:

1. To study the quality of life of patients suffering from chronic prostatitis.

2. To investigate the features of free radical processes and immunoreactivity in patients with chronic bacterial and abacterial prostatitis.

3. To investigate the content of cytokines and secretory immunoglobulin A in the ejaculate of patients with chronic bacterial and abacterial prostatitis.

4. To evaluate the sensitivity and specificity of parameters of free radical processes and immunoreactivity in the diagnosis of chronic prostatitis.

5. To investigate the effect of glucosaminylmuramyl dipeptide (lycopide) on immunological indicators in patients with chronic bacterial and abacterial prostatitis, and to evaluate the efficacy of immunomodulatory therapy in the complex treatment of patients with chronic prostatitis.

Scientific Novelty.

It has been established that the leading pathogenetic factors of the recurrent course of chronic prostatitis are the suppression of free radical oxidation processes and the immunoreactivity of the organism. New data have been obtained on the sensitivity and specificity of immunophenotyping of blood lymphocytes, the content of complement system components, and the cytokine profile of ejaculate for the diagnosis of chronic prostatitis.

Pathogenetic associations between the clinical variant of the disease and immunological changes have been established. A method for diagnosing abacterial chronic prostatitis based on the content of lymphocyte subpopulations in the blood has been developed (priority patent application No. 2009124509 dated 06/26/2009).

It has been found that in both bacterial and abacterial prostatitis, hyporeactivity of the immune system, suppression of active oxygen species production, and cytokine imbalance in the ejaculate are observed, leading to prolonged ongoing inflammation in the prostate gland.

Practical Significance.

The results of the conducted research indicate the occurrence of changes in the immune system in chronic bacterial and abacterial prostatitis, persisting over time, associated with the form of the disease, and regressing under the influence of immunomodulatory therapy. A list of the most informative tests for detecting immune system disorders in patients with chronic prostatitis has been determined. Methodological recommendations titled "Efficacy of Lycopide Use in Patients with Chronic Prostatitis" have been published.

Principal Conclusions to be Defended

1. The leading pathogenetic factors of chronic bacterial and abacterial prostatitis are the suppression of free radical processes and the disruption of various components of the immune system.

2. Standard therapy for chronic prostatitis does not possess sufficient efficacy, as an immunodeficient state continues to persist in patients after treatment.

3. Immunocorrective therapy using glucosaminylmuramyl dipeptide (lycopide) leads to the normalization of most altered indicators of immunological reactivity, is accompanied by high clinical efficacy, and exerts a preventive effect with regard to disease relapses.

Implementation of the Research Results.

The results of the work are used in the clinical practice of the urology department of the Budgetary Institution of Healthcare of the Omsk Region "Clinical Medical-Surgical Center of the Ministry of Healthcare of the Omsk Region", the Budgetary Institution of Healthcare of the Omsk Region "Clinical Diagnostic Center", and in the educational process at the Department of Pathophysiology with a course in clinical pathophysiology of the Omsk State Medical Academy.

Validation of the Research Results.

The principal provisions of the work were reported and discussed at the Inter-University Conference of Young Scientists "Current Problems of Pathophysiology" (Saint Petersburg, April 2006); the International Congress on Andrology (Sochi, May 2006); the XIV Inter-City Conference of Young Scientists "Current Problems of Pathophysiology" (Saint Petersburg, April 2008); the Scientific and Practical Conference "Clinical and Fundamental Aspects of Critical States" (Omsk, May 2008); the Interregional Conference "Modern Issues of Urology, Andrology, and Reproductive Medicine" (Novosibirsk, 2008); the International Congress on Andrology (Sochi, May 2009); the XV Inter-City Conference of Young Scientists "Current Problems of Pathophysiology" (Saint Petersburg, April 2009).

Publications. Nine works have been published on the dissertation topic, including 2 articles in journals listed in the VAK of the Ministry of Education and Science of the Russian Federation.

Structure and Volume of the Dissertation.

The dissertation consists of an introduction, a literature review, two chapters containing the results of original research, a conclusion (discussion of the research results), and conclusions. The manuscript comprises 175 pages, illustrated with 81 tables and 23 figures. The bibliography contains 210 works (130 sources in Russian and 80 foreign sources). All materials presented in the dissertation were obtained, processed, and analyzed personally by the author.