EVALUATION OF THE EFFECTIVENESS OF IMMUNOPROPHYLAXIS IN DISSEMINATED PERITONITIS

SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 214 EVALUATION OF THE EFFECTIVENESS OF IMMUNOPROPHYLAXIS IN DISSEMINATED PERITONITIS O.U. Rakhimov1, Sh.T. Tirkashev2, J.R. Kamoljonov3, S.Sh. Mirzayev4 Tashkent State Medical University1,2,3,4 https://doi.org/10.5281/zenodo.17538689 Abstract. Generalized peritonitis is accompanied by severe immune system dysfunction, which increases the risk of postoperative complications and mortality. This study assessed the clinical and immunological efficacy of personalized immunoprophylaxis in 60 patients with varying degrees of risk for complications, assessed using the IPORP scale. Use of the IPORP algorithm allows for differentiation of immunocorrection approaches depending on the severity of the immunopathology, providing a pathogenetically substantiated, personalized strategy for the prevention of complicated peritonitis. Keywords: generalized peritonitis, immunoprophylaxis, IPORP, CD4⁺ T-helpers, NK cells, IgM, immunocorrection, cytokines, circulating immune complexes. Introduction. It has been scientifically established that treatment of generalized peritonitis (GP) includes optimal surgical management and comprehensive intensive care. Despite the study of pathogenesis, the systemic inflammatory response, and modern methods of organ debridement and support, issues of early outcome prediction and identification of patients at high risk of complications remain unresolved. This justifies the need for further clinical and immunological research and the development of new prognostic algorithms [1,8]. Treatment of disseminated peritonitis includes optimal surgical tactics and comprehensive intensive care. Key pathogenesis factors, methods of abdominal debridement, antibacterial therapy, and organ support have been studied. Nevertheless, rates of complications and mortality remain high, indicating unresolved clinical issues [2,5]. The use of immunomodulatory agents in peritonitis is limited due to the lack of uniform approaches to indications and efficacy assessment. This emphasizes the need for further clinical and immunological research and the inclusion of immunological parameters in the standard care of such patients [3,6]. The high complication rate of disseminated peritonitis and impaired immune homeostasis highlight the need to develop a prognostic model based on immunological markers. Early detection of immunopathological changes and individualized immunoprophylaxis can reduce the risk of complications, improve treatment outcomes, and increase patient survival [4,7]. Aim of the research: For evaluating the clinical and immunological efficacy of personalized immunoprophylaxis in patients with disseminated peritonitis, depending on the severity of immunopathological changes and the prognostic risk of complicated postoperative course, with the aim of stabilizing the inflammatory process and reducing the incidence of complications. Materials and Methods: The study included 60 patients with disseminated peritonitis, categorized by risk of complicated course using the IPORP scale: low (<10 points), high (10–19 points), and critical (≥20 points). The mean age of patients was 52.4 ± 14.7 years (range: 22–78 years), the male-to-female ratio was 32/28. The control group consisted of conditionally healthy donors (n=20) for comparison of immunological parameters. SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 215 Immune status assessment included a study of the cellular and humoral immune systems: - Cellular immunity: CD3⁺, CD4⁺, CD8⁺ T lymphocytes, NK cells (CD16⁺CD56⁺), determination of absolute count and percentage; - Humoral immunity: IgA, IgM, IgG; - Cytokine profile: IL-6, IL-10; - Circulating immune complexes (CIC). Immunological parameters were assessed before therapy and on days 3 and 7 postoperatively. Patients in the study group received individualized immunoprophylaxis depending on their risk level: Low risk (<10 IPORP points): "wait and see" management—observation, maintenance of natural immune balance, nutritional and electrolyte adjustments, and limitation of systemic antibiotic therapy. High risk (10–19 points): basic immunoprophylaxis, including thymic immunomodulators (Thymalin 10 mg intramuscularly once daily for 5–7 days or T-activin 1 mcg/kg subcutaneously for 5 days), intravenous IgM-enriched immunoglobulin (Pentaglobin 5 ml/kg/day for 2–3 days), antioxidants (vitamins A, E, C). Critical risk (≥20 points): extended immunocorrection complex — polyvalent IgM/IgA (Pentaglobin, IgM Octagat 5 ml/kg/day for 3–5 days), thymic stimulants, anti-cytokine agents for severe cytokine imbalance, levamisole, and immunomodulatory heparin. The effectiveness of the intervention was assessed by changes in CD4⁺, NK, IL-6, IL-10, IgM, and circulating immune complexes (CIC), as well as clinical indicators: restoration of homeostasis, reduction in signs of intoxication, and the incidence of postoperative complications. The statistical data processing was performed using standard descriptive statistics, correlation analysis, and comparative tests for dependent and independent samples. Differences were considered significant at p<0.05. Results and discussion. Patients with an IPORP score of less than 10 had isolated, minor immune abnormalities within the physiological norm: CD4⁺ T helper cells >0.60×10⁹/L, NK cells ~0.25×10⁹/L, IgM 0.9-1.1 g/L, IL-6 ≤30 pg/ml, CIC <55 opt. Units. Clinically, the reactive phase of peritonitis with serous or serofibrinous exudate predominated, without generalized inflammation or intoxication, with rapid restoration of homeostasis and a low risk of complications. International data show that immunotropic therapy in the absence of immunosuppression and predictors of adverse outcomes can be excessive and even harmful. Therefore, a "wait-andsee" approach was used in low-risk patients: observation and maintenance of natural immune balance, discontinuation of immunotropic agents, adjustment of nutrition and fluid and electrolyte balance, and limitation of systemic antibiotic therapy in the absence of infection. There were no deaths in this group, and the complication rate was ≤11%. It is crucial to acknowledge that patients with IPORP scores of 10-19 show signs of initial immunosuppression within the first 24 hours after surgery: CD4⁺ T-helper cells 0.41-0.60×10⁹/L, NK cells down to 0.25×10⁹/L, and IL-6 down to 60 pg/ml. These changes indicate weakened Tcell cooperation, impaired innate cytotoxic control, and activation of the proinflammatory cytokine cascade. In the early postoperative period, effective interventions can be implemented to stabilize the inflammatory environment and prevent systemic dysfunction. High-risk patients received pathogen-targeted immunoprophylaxis aimed at supporting Tand B-cell immunity and limiting mediator hyperreaction. The regimen consisted of thymic immunomodulators (thymalin 10 mg intramuscularly once daily for 5-7 days or T-activin 1 mcg/kg subcutaneously for 5 days), which SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 216 promote the proliferation of CD4⁺ T-helper cells and restore cooperation with B-cells. The use of these drugs reduced the incidence of infectious complications by more than 30%. The humoral support was maintained with intravenous IgM-enriched immunoglobulin (Pentaglobin) at a dose of 5 ml/kg/day for 2-3 days. IgM supplementation improves opsonization, reduces circulating immune complexes, and stabilizes the complement-dependent immune response. Antioxidant support was provided with vitamins A (100,000 IU intramuscularly), E (300 mg orally), and C (500-1000 mg intravenously). It is generally recognized that efficacy was assessed on days 3 and 7 based on CD4⁺, NK, IL-6, IgM, and circulating immune complexes. If immunosuppression progressed, expanded immunotherapy was prescribed. Patients with an IPORP score ≥20 had significant immunopathological changes: CD4⁺ ≤0.40×10⁹/L, NK ≤0.17×10⁹/L, IgM ≤0.60 g/L, IL-6 >90 pg/ml, IL-10 >20 pg/ml, CIC >75 optical units, which corresponded to the terminal phase of peritonitis and a high incidence of multiple organ dysfunction. This condition is interpreted as post-aggressive immunosuppression with depletion of innate and adaptive immunity. It is important to clarify that for critically ill patients, an expanded regimen was used: polyvalent IgM/IgA (Pentaglobin, IgM Octagat) 5 ml/kg/day IV for 3-5 days; in cases of severe cytokine imbalance, anti-cytokine agents as indicated, thymic stimulants, levamisole, and immunomodulatory heparin. Daily monitoring of IL-6, IL-10, CD4⁺, NK, circulating immune complexes (CICs), and IgM allowed for tailored intervention. The IPORP-based algorithm allowed for the identification of three risk levels: low (<10), high (10–19), and critical (≥20 points), and individualized immunotherapy. Low-risk patients received an immune abstinence strategy; high-risk patients received basic immunoprophylaxis with thymic peptides, IgM immunoglobulins, and antioxidants; and critical patients received an expanded regimen with intensive immunotherapy. The algorithm's fundamental distinction is its pathogenetic focus: compensating for immune deficiencies, blocking hypercytokinemia, and preventing the progression of the inflammatory cascade to multiple organ failure and septic complications. IPORP has enabled the transformation of immunoprophylaxis into a manageable, personalized system that reflects the severity of immunopathology and its reversibility (Table 1). Table 1 Comparison of immune response indicators and immunoprophylaxis strategies depending on the risk of complications Risk level (IPORP) Number of points Immunological indicators Clinical picture Immunoprophylaxis tactics Low <10 CD4⁺ >0.60×10⁹/l, NK ~0.25×10⁹/l, IgM 0.9–1.1 g/l, IL6 ≤30 pg/ml, CEC <55 Reactive phase, serous/serofibrinous exudate, without generalization Expectant management, maintaining immune balance, adjusting nutrition and waterelectrolyte balance, limiting antibiotics High 10–19 CD4⁺ 0.41– 0.60×10⁹/L, NK ↓ up to 0.25×10⁹/L, IL-6 up to 60 pg/ml Initial immunosuppression, proinflammatory cascade Thymalin/T-activin, IgM immunoglobulin, antioxidants SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 217 Critical ≥20 CD4⁺ ≤0.40×10⁹/l, NK ≤0.17×10⁹/l, IgM ≤0.60 g/l, IL-6 >90 pg/ml, IL-10 >20 pg/ml, CEC >75 Terminal phase, high incidence of multiple organ dysfunction Extended regimen: IgM/IgA, anti-cytokine agents, thymic stimulants, levamisole, heparin The evidence clearly shows that before inclusion in the immunoprophylaxis regimen, most patients in the study group demonstrated significant suppression of cellular immunity, comparable to the control group. All patients were classified as high or critical risk on the IPORP scale, clinically corresponding to toxic or terminal peritonitis and accompanied by severe immunological disorders. The most significant difference was the CD4⁺ T-helper cell level: an average of 0.34×10⁹/L with a normal value of 1.01×10⁹/L, with 12 patients having levels ≤0.30×10⁹/L (Table 2). Table 2 Cellular immunity status in study group patients before and after immunocorrection compared to normal values INDICATOR REFERENCE (n=20) IMMUNOPROPHYLAXIS Before (n=60) After (n=60) Lymphocytes, % 28,2±3,6 17,1±3,9* 25,6±4,1*# Lymphocytes, ×10⁹/л 2,16±0,52 0,91±0,28* 1,84±0,34*# CD3+, % 68,4±4,3 49,2±5,7* 64,7±4,6*# CD3+, ×10⁹/l 1,65±0,37 0,66±0,22* 1,43±0,29*# CD4+, % 40,1±4,9 26,1±4,3* 37,8±4,4*# CD4+, ×10⁹/l 1,01±0,28 0,34±0,11* 0,87±0,18*# CD8+, % 25,3±3,2 20,4±3,4* 24,1±3,3# CD8+, ×10⁹/l 0,66±0,14 0,29±0,09* 0,52±0,12*# CD4+/CD8+ 1,65±0,21 1,19±0,15* 1,52±0,17# CD16+/CD56+, % 14,8±2,5 9,2±2,0* 13,7±2,1# CD16+/CD56+, ×10⁹/l 0,31±0,06 0,16±0,05* 0,27±0,06# Note: * - p<0.05 statistically significant value relative to reference values; # - p<0.05 statistically significant value relative to patients before immunoprophylaxis. In one such situation, a 63-year-old man who underwent surgery for pancreatic necrosis continued to experience severe intoxication on the second postoperative day, despite normalizing temperature readings. An immunogram revealed CD4⁺ 0.26×10⁹/L, CD3⁺ 0.58×10⁹/L, and CD16⁺CD56⁺ 0.12×10⁹/L. The patient was transferred to an extended immunotherapy regimen. It is widely supported by data that before the start of immunoprophylaxis, the patients had significant lymphocyte suppression. The average lymphocyte count in the white blood cell count was only 17.1%, almost 1.7 times lower than that of healthy controls (28.2%). In absolute terms, the decrease was even more significant: the lymphocyte concentration was 0.91×10⁹/L versus the reference value of 2.16×10⁹/L, or 2.4 times lower than normal. The CD3⁺ T-lymphocyte count (a key population of adaptive immunity) decreased by 2.5 times, from 1.65 to 0.66×10⁹/L, indicating systemic suppression of T-cell activity. Although the level of CD8⁺ T-suppressors also decreased by almost 2.3 times, the magnitude of this decrease was less significant than that of cooperative CD4⁺ T-helper cells. This SCIENCE AND INNOVATION INTERNATIONAL SCIENTIFIC JOURNAL VOLUME 4 ISSUE 10 OCTOBER 2025 ISSN: 2181-3337 | SCIENTISTS.UZ 218 led to an imbalance between regulatory and effector components, as directly indicated by the change in the CD4⁺/CD8⁺ ratio: it decreased by 28%. This dynamic reflects not simply a quantitative deficit, but a qualitative failure of immune response regulation, characteristic of the initial immunosuppression phase in severe surgical site infections. It is broadly accepted that particular attention should be paid to the innate immune system, especially natural killer cells, characterized by CD16⁺CD56⁺. Before immunoprophylaxis, their values were more than half the reference value, indicating a pronounced deficiency in the cytotoxic component. In more than half of the patients, the level of these cells remained critically low (less than 0.20 × 10⁹/L). For example, a 72-year-old man with surgical treatment for fecal peritonitis secondary to a colon tumor had a CD16⁺CD56⁺ cell population of 0.11 × 10⁹/L, and three days later, he developed a postoperative wound infection and inflammatory complication. After completing a personalized course of immunoprophylaxis, accelerated cellular regeneration was consistently observed. The absolute lymphocyte count increased almost twofold, and the CD3⁺ T-lymphocyte count matched the control level. Notably, CD4⁺ T-helper cells, which play a key role in adaptive immunity, increased more than 2.5-fold, and the CD4⁺/CD8⁺ ratio returned to near-normal levels, indicating a significant restoration of homeostasis. The function of CD16⁺CD56⁺ cells is interesting: after treatment, their count increased by approximately 1.7-fold, and at this level, a significant improvement in the patient's clinical condition was observed in most cases (signs of intoxication decreased, hemodynamics stabilized, and body temperature returned to normal). This coincided with a decrease in PCT concentrations and the systemic inflammatory phase in 75% of patients. Conclusion. As for the aforementioned patient with pancreatic necrosis, on day 7 of his illness, the CD4⁺ count almost reached the lower limit of normal, coinciding with the restoration of cytotoxic NK cells and a reduction in inflammatory symptoms. The patient was safely transferred to the recovery ward without complications. It is commonly understood that these results demonstrate that immunoprophylaxis against pathogenetically sensitive components of the immune response compensates not only for quantitative deficits but also for functional coordination within the T-helper and innate effector cell systems, leading to an improved inflammatory response and a reduced risk of complications. In the early stages of immunotherapy, patients with high and critical risk of complications demonstrated significant impairment of humoral immunity. The average IgM level was approximately one-third of normal, and in some patients it decreased to 0.65–0.70 g/L, especially in patients with severe pancreatic necrosis and fecal peritonitis, which is almost half the physiological norm. REFERENCES 1. Rakhimov O., Tirkashev S., Rashidov Z. Features of the postoperative period after laparoscopic cholecystectomy // Science and innovation. – 2024. – Vol. 3. – No. D5. – P. 387393. 2. Abdumazhidov A. Sh. et al. 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