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Suleymanov Suleyman Fayzullaevich, PhD., Senior Researcher, Associate Professor, of the Chair of Microbiology and Pharmacology of the Bukhara State Medical Institute, Bukhara, Uzbekistan E-mail: [email protected]
IMPAIRED IMMUNE HOMEOSTASIS AND ITS CORRECTION IN PATIENTS WITH CHRONIC CHOLECYSTITIS
Abstract: Immune system was analyzed in 55 patients with Chronic Cholecystitis (CC) and 36 healthy individuals. Patients identified suppression of T-Systems and its subpopulations, voltage moral immunity. Traditional methods of treatment did not lead to the elimination of the immunodeficiency in patients with chronic cholecyctitis.
Thymoptinum a total dose of 1.0 mg - 1.2 mg (per course), applied in 21 patients with chronic cholecyctitis eliminated immune disorders, raised the entire spectrum of cell-mediated immunity, possessed immune correction and therapeutic effect.
Keywords: chronic cholecistitis, immune status, immunodeficiency, immunocorrection, thy-moptinum.
Chronic Cholecystitis (CC) is the most common pathology among time-personal hepatobiliary diseases zone and does not tendency to decrease. Disorders of the immune status, detected in chronic inflammatory diseases of the nutritional-rhenium, in a certain way influence the course of the disease, contribute to chronicity of inflammation-reducing process and eventually repair mechanisms. Shifts in the immune system can lead to the development of CC [5, 6, 13, 14].
The aim of the study was to determine the main parameters of the immune system and checking immune correction in patients with CC.
Materials and methods. Indicators of immune system have been studied in 55 patients with a diagnosis of CC in an exacerbation stage aged 38 to 72 years, of which 38 were women (69.1%) males - 17 (30.9%). In 24 (43.6%) patients had concomitant diseases: Chronic Gastritis - 9, Chronic Pancreatitis - 7, Chronic Peptic Ulcer of the Stomach - 4, Chronic Ulcer Duodenum - 2, Duodenitis - 2. 21 (38.1%) patients were operated for Chronic Calculous Cholecystitis, the rest - 34 (61.8%) -were treated conservatively.
Diagnosis CC was based on data of the clinical picture of the disease and the results of laboratory by instrumental methods.
Phenotyping of lymphocytes was performed by indirect immunofluorescence method with monoclonal antibodies to the receptors of CD-production «Sorbent Ltd» Institute of Immunology, Ministry of Health of the Russian Federation on the microscope "Luminal P-8." T cells was determined (total population - CD3); helper T cells (a subset of Th - CD4); T-suppressors (a subset of Ts - CD8); B cells (a subset of CD19) and Immuno-regulatory Index (IRi) - the ratio of CD4 / CD8 [12].
The concentration of serum immunoglobulins (SI) classes A, M and G were determined by radial immunodiffusion [9], the level of circulating immune complexes (CIC) - method precipitation [1], and the values were expressed in optical density units (opt.dens.un.). Immunological examination was carried out for 2-5 hours after hospital admission and 1 month after treatment. The control group for comparison immunologi-cal figure was 36 healthy subjects (25-55 years). The drug Thymoptinum (Uzbekistan) received 19 (34.5%) patients with CC.
Efficacy was assessed by immunotherapy dynamics immunological indices in comparison with the same data before the treatment by the formula:
Ki = [(B - A)/A] x 100%, where Ki is - immune index; A - immunological parameters before treatment;
B - treatment after immunological parameter. Immune correction considered effective when Ki > 10%.
Statistical processing of the data was carried out on Pentium-IV computer with using program Exel Statistic (Version 6.0) for Windows. The significance of differences on comparison meaning values was determined by Student's t test. Data are presented as M ± m. Differences were considered significant at p < 0.05.
Results and discussion. Results of the study of the immune system parameters in patients with CC presented in the (Table 1, 2), and indicate an imbalance in the functioning of the immune system. In CC was found a decrease in the relative size of T (CD3) cells (p < 0.001). At the same time watched first degree by A. M. Zemskov disorders (-31.3%) [17]. The results indicate a significant reduction in the blood in patients fraction of Ts (of CD8) (p < 0.001), a mo-derate reduction in the level of Th
(CD4) (p > 0.05) and the inversion of the IRI, which was reflected in its increase (Table 1). The relative magnitude (of CD19) lymphocytes was sta-tistically higher than the control group values (p < 0.01) (Table 1).
Patients with chronic cholecyctitis marked shortage ofbasic parameters ofhumoral immune system: IgA and IgM (Table 2). In this group occurred IgG increase more significantly - CIC (p < 0.001).
We suppose that increasing the concentration of IgG and CIC in patients with CC occurs due to the presence of a constant source of inflammation in the gallbladder. Reduction in blood
T (CD3) - lymphocytes, and maintaining at the same time a high level of IgG and CIC at this pathology indicates that the inflammatory process in the gastrointestinal tract has not been completed and its chronization takes place [7, 8].
Table 1.- Dynamics of cellular immunity in patients with CC disease in process of immune correction treatment (M ± m)
Indicators Patients with CC Healthy patients
CD3 (%) A 35.3 ± 1.8*** 51.2 ± 1.7
B 52.4 ± 2.2
CD4 (%) A 31.3 ± 1.3 35.8 ± 0.7
B 34.8 ± 1.7
CD8 (%) A 10.7 ± 0.8*** 17.4 ± 1.2
B 13.1 ± 0.6***
IRI A 2.88 ± 0.17*** 2.16 ± 0.10
(CD4/CD8) B 2.63 ± 0.21*
CD19 (%) A 18.7 ± 1.4** 14.8 ± 0.9
B 21.3 ± 1.6**
Note: A - indicators before treatment, B - indexes after treatment; * - P < 0.05; ** - P < 0.01; *** - P < 0.001 compared to the control
Evidently, increasing the amount concentration of IgG in patients is due to zone presence of antigens as a permanent "focus excitation" in these as relates to the IgG antibodies are actively functioning, with the direct participation of which agglutination and lysis of foreign agents[5-8, 10].
A significant increase in the index of the CIC in patients with CC in the blood and tissues leads to what is happening in the tissues of a metabolic disorder that is causing degeneration and regeneration mechanisms in the gallbladder [13, 14, 16].
Thus, patients with CC has the following changes in their immunogram: decreasing CD3, CD4, CD8 cells; increasing in CD19; decrease levels of IgA and IgM; increase in IgG and CEC. Changes in the im-
mune system suggests that patients had to identify immunodeficiency, especially on the part of the T-immunity. Apparently, immunodeficiency state by nature is secondary. To eliminate immune disorders drug thymoptinum (Uzbekistan) was used as an adjunct to conventional treatment conducted, which included conservative therapy and operator-porate intervention treatment conducted, which included conservative therapy and surgery.
Analysis of the clinical and immunological and laboratory instrumental research methods, depending on the used treatments pointed to favorable for pathologists-agency process in patients when applying immune correcting treatment.
Table 2.- Dynamics of humoral immunity in patients with CC disease in process of immune correction treatment (M ± m)
Indicators Patients with CC Healthy patients
IgA, g/l A 1.81 ± 0.62 2.82 ± 0.31
B 1.45 ± 0.74
IgM, g/l A 1.27 ± 0.22 1.64 ± 0.11
B 0.90 ± 0.36*
IgG, g/l A 18.60 ± 1.40 15.90 ± 0.94
B 15.74 ± 1.26
CIC A 0.174 ± 0.04*** 0.046 ± 0.006
(opt.dens.un.) B 0.190 ± 0.032***
Note: A - indicators before treatment, B - indexes after treatment; * - P < 0.05;** - P < 0.01; *** - P < 0.001 compared to the control.
The generally accepted standard treatment (Surgery + Therapy), conducted in 36 patients, did not lead to the restoration of disturbed immune status indicators. For example, after treatment the relative number of CD3 was 37.6 ± 1.5% and was statistically lower than those values of the control group (p < 0.001), the greatness ofCD19-on amounted to 16.2 ± 0.7% (p > 0,05), the concentration of SI consisted: IgA - 1.92 ± 0.74% g/l, IgM - 1.21 ± ± 0,34 g/l, IgG - 17.45 ± 1.31 g/l and did not reach the background level of the control group(p > 0.05). Number of CIC tended to increase 0.183 ± 0.045 opt.dens.un.
Introduction to the scheme of combined treatment of patients with CC Thymoptinum led to an increase in cellular and humoral immunity. Under the influence of Thymoptinum hap-pening efficiency increase initially reduced values of the immune system. It was registered statistically significant increase in the total pool of T cells (phenotype of CD3), B-lymphocytes (of CD19) (p < 0.001), as well as IRI decline with an increase in the proportion of Ts (of CD8), which is certainly, a predictor of the effectiveness of immunotherapy CC, as it leads to a dec-rease, in the intensity of autoimmune processes (Table 1).
This Ki for CD3 cells was 48.4% and for B-lymphocytes (CD19) - 13.9%, which is undoubtedly a reflection of the positive dynamics of the changes carried out by immunocor-rection.
In addition, there was a trend to decrease IgG (p > 0.05) in the course of immunotherapy, but IgM and IgA remained low (Table 2).
Our data on the number of positions is quite consistent with the results of other resear-chers [5, 8, 16].
It is known that in chronic diseases of the gallbladder and biliary tract are non-specific pathogenic mechanisms, as hypoxia, tissue destruction, production of endogenous toxins are an important pathogenetic link, resulting in aggregate, of a violation of the function of the thymus and secondary immunodeficiency states, and this, in turn, contributes to the chronicity of the pathological process in the gall bladder [3, 4, 11, 15, 16].
Conclusions:
1. In CC observed deep depression T-immunity in the functioning of humoral immunity.
2. Traditional methods of treatment did not lead to the restoration of disturbed parts of the system that we have immunity in patients with CC.
3. Application Thymoptinum as a corrector of disorders of the immune system in pa-tients with CC contributed to the effective elimination of disorders of cellmediated immunity (T-lymphocytes), as evidenced by Ki factors, and reduce stress in humoral component of the immune system. Immunomoduline possess immunomodulatory effects in patients with CC.
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