CC BY
0IMMUNOLOGICAL FEATURES OF THE INFLAMMATORY PROCESS IN CHILDREN WITH HEMOCOLITIS SYNDROME
OF DIFFERENT SEVERITY
Khudayberdiyeva Ch.K.
PhD student of Tashkent Pediatric Medical Institute https://doi.org/10.5281/zenodo.13884938
Abstract. It is important to suggest that hemocolitis syndrome (HSS) in children is a serious pathology associated with inflammatory processes in the intestine and activation of the immune response. This study is devoted to the analysis of immune mechanisms involved in the development of acute diarrheal syndrome with hemocolitis in children aged 6 months to 5 years. The studied indicators of nonspecific immune response and cytokine profile allow us to identify significant changes in both proinflammatory and anti-inflammatory mechanisms. The results demonstrate the activation of the inflammatory process in children with varying severity of HSS and can be useful for developing new approaches to therapy.
Keywords: pediatric gastroenterology and immunology, therapy.
INTRODUCTION. It is known to everyone that immune mechanisms play a key role in the development and severity of inflammatory reactions in the intestine. Disturbances in the functioning of the cellular and humoral components of the immune system, as well as changes in the level of cytokines, can enhance the inflammatory process, which leads to tissue damage and the development of systemic complications [1,6]. Hemocolitis syndrome (HC) in young children is a pressing issue in pediatric gastroenterology and immunology. This disease is characterized by inflammatory changes in the intestine, leading to damage to the mucous membrane and systemic complications [1, 3]. Studies of the immune response in children with HC are especially important at the age of 2-5 years, which refers to the third critical period of immune system development according to J.V. Solomon, when active formation of adaptive immunity occurs [2].
Surprisingly, recent studies have shown that acute diarrhea (AD) is accompanied by hyperactivation of the immune system, which leads to damage to the intestinal mucosa and the development of severe inflammatory changes [2,5]. Given the increasing prevalence of intestinal infections and the resistance of microorganisms to traditional antibiotics, the study of immune responses in such conditions is necessary to develop new treatment methods that could effectively control the inflammatory process and prevent its complications. Based on the above, the aim of this study was to analyze the characteristics of the nonspecific immune response and cytokine profile in children with varying severity of hemocolitis syndrome.
MATERIALS AND METHODS. During the study, 120 children aged 6 months to 5 years with an established diagnosis of hemocolitis syndrome were examined, who were divided into two groups according to the clinical manifestation of the disease: with mild (n = 23) and moderate (n = 95) course of SG. The control group consisted of 25 practically healthy children of similar age.
Besides that, immunological studies were conducted in the Experimental Immunology laboratory of the Institute of Human Immunology and Genomics of the Academy of Sciences of the Republic of Uzbekistan.
Determination of serum levels of non-specific factors (CRP, PCT), immune response mediators (IL-4, IL-6, IFN-y) and vascular endothelial growth factor (VEGF-A) was performed by solid-phase enzyme immunoassay using test systems of JSC VECTOR-BEST (Russia), in accordance with the manufacturer's recommendations. Quantitative assessment of the results was performed by constructing a calibration curve reflecting the dependence of optical density on concentration for a standard antigen and allowing comparison of the studied samples with it.
Statistical processing of the research results was carried out by the methods of variation statistics implemented by the standard package of applied programs "BioStat LE 7.6.5". The data were statistically processed using conventional approaches, the results are presented as the sample mean (M) and the standard error of the mean (m). The reliability of differences in the mean values (P) of the compared indicators was assessed by the Student's criterion (t).
RESULTS. Innate humoral factors of the immune response are components of the innate immune system that quickly and without prior exposure to the pathogen protect the body. They circulate in the blood and intercellular fluid, providing the first line of defense before the activation of adaptive immunity [4]. Studying these factors in children with different courses of hemocolitis helps to understand the mechanisms of protection and identify markers that predict the transition of the disease to a more severe form.
Table 1.
Parameters of non-specific immunity factors in the examined children with HS.
Indicator Control Group, Mild HS, Moderate HS, (n=95)
(n=25) (n=23)
CRP, mg/l 3,51±1,42 9,83±1,78** 15,61±3,22***
PCT, ng/ml 0,25±0,17 0,64±0,43A 0,89±0,61A
Note: * - values are reliable in relation to the data of the control group (* - P<0.05, ** -P<0.01, *** - P<0.001). A - values are not reliable in relation to the data of the control group (A -P>0.05).
According to the analysis of the obtained results, in the group of children with mild HS, there was a significant increase in the CRP level by 2.8 times (P < 0.01), which indicates an active inflammatory process. In the moderate HS, the CRP level was almost 4.5 times (P < 0.001) compared to the control group, which also indicates a high degree of the inflammatory process in children with hemocolitis (Table 1).
The PCT level in both groups was also increased by 2.5 and 3.6 times, but statistically significant differences were not detected during the study (P > 0.05).
Cytokines, as signaling molecules, play a key role in coordinating the immune response, and their levels can reflect the degree of inflammation and predict possible complications [4,5]. The study of the cytokine profile in children with different courses of hemocolitis is of critical importance, especially at the age of 6 months to 5 years, when the immune system is actively developing and forming, and allows for a detailed assessment of the inflammatory and regulatory mechanisms that control the body's response to the pathogen.
The results of the cytokine response in this sample of children are presented in Table 2
below.
Moreover, analysis of the cytokine status showed significant changes in the levels of the studied cytokines in children with HS compared to the control group.
Thus, in children with mild HS, the level of IL-6 was 2 times higher (P < 0.05), IFN-y - 1.7 times (P < 0.01), and VEGF-A - 1.9 times (P < 0.001) compared to the indicators of practically healthy children in the control group (Table 2).
Table 2.
Serum content of the studied mediators of the immune response in the examined children with
SG.
Indicator, pg/ml Control group,(n=25) Mild course of SG, (n=23) Moderate course of SG, (n=95)
IL-4 2,39 ±0,87 5,86 ±0,49*** 1,63 ±1,47A
IL-6 3,51±1,93 7,03±0,45* 9,28±1,39**
IFN-y 12,59±2,18 21,68±2,51** 25,01±1,71***
VEGF-A 169,57±16,87 320,29±30,09*** 390,57±19,57***
Note: * - values are reliable in relation to the data of the control group (* - P<0.05, ** -P<0.01, *** -P<0.001).
It was also found that in children with moderate HS, the synthesis of the levels of the studied cytokines was increased: IL-6 by almost 2.6 times (P < 0.01), IFN-y by 2 times (P < 0.001), VEGF-A by more than 2.3 times (P < 0.001) (Table 2).
Definitely, the analysis of the serum content of the anti-inflammatory cytokine IL-4, on the contrary, showed multidirectional changes. Thus, if the concentration of IL-4 in the group of children with mild HS was 2.45 times higher than in the control group (P<0.001), then the level of this interleukin was reduced in children with moderate HS by 31.8%, which is 1.5 times lower than the level in the control group (P>0.05) (Table 2).
DISCUSSION OF THE RESULTS OBTAINED. It should be suggested that the study of innate humoral factors of the immune response, such as CRP and PCT, in combination with cytokine profile analysis, provides a more complete understanding of the pathogenesis of inflammatory processes in hemocolitis syndrome, since the studied biomarkers allow us to assess the degree of inflammation. CRP, synthesized in response to inflammation and activated by proinflammatory cytokines [6], reflects acute inflammation, and its significant increase detected in children with various forms of HS indicates the presence of a pronounced inflammatory process.
Procalcitonin (PCT), although more specific for bacterial infections, also increases in severe inflammatory reactions [1]. It is important to note that its level in this study did not reach statistical significance, which may indicate that the inflammatory process in SG is not always bacterial in nature, especially in mild forms, which probably confirms the hypothesis that inflammation in hemocolitis can be caused by other factors not associated with bacterial agents. Cytokines play a key role in the regulation of the inflammatory response [4]. IL-6, one of the main proinflammatory cytokines, stimulates the synthesis of CRP [4,5], which confirms the relationship between the cytokine profile and CRP levels. The observed increase in IL-6 and IFN-y in children with hemocolitis reflects enhanced activation of the cellular immune response. Considering that IFN-y, by activating macrophages and enhancing antigen presentation, contributes to the intensification of the inflammatory process and can lead to tissue damage during chronic inflammation [5,7], we admit the probable fact that an increase in the levels of these cytokines correlates with the severity of the inflammatory response, which can be confirmed by high levels of CRP.
On the other hand, VEGF-A, an angiogenic factor, stimulates the restoration of the vascular network in response to tissue damage [4], but its significant excess can aggravate inflammation by increasing vascular permeability, which is also confirmed in children with more severe forms of HS.
A decrease in the level of IL-4 in children with severe forms of HS indicates a deficiency of anti-inflammatory mechanisms, which leads to an imbalance between pro- and anti-inflammatory processes. Probably, the imbalance contributes to the progression of inflammation and complications of the disease.
Thus, the imbalance between IL-6, IFN-y, VEGF-A and IL-4 cytokines in children with hemocolitis syndrome confirms the complexity of the pathogenesis of this disease. These changes can be used as markers for assessing the severity of the inflammatory process and developing more targeted therapeutic strategies aimed at correcting immune disorders and restoring the balance between inflammatory and anti-inflammatory mechanisms.
CONCLUSION. By summarizing it should be suggested that the immunopathogenesis of hemocolitis syndrome in children is associated with a pronounced imbalance of proinflammatory and anti-inflammatory mechanisms, which is reflected in an increase in the level of CRP, IL-6, IFN-y and VEGF-A.
The combination of the analysis of innate humoral factors, such as CRP and PCT, with the cytokine profile allows for a deeper understanding of the pathogenesis of inflammation in hemocolitis syndrome in children. The studied biomarkers can be used to predict the severity of the inflammatory process and develop more targeted therapeutic approaches aimed at balancing proinflammatory and anti-inflammatory mechanisms.
REFERENCES
1. Gonchar N.V., Ermoolenko K.D., Klimova O.I., Ermoolenko E.I., Gostev V.V., Lobzin Yu.V. Bacterial intestinal infections with hemocolitis syndrome in children: etiology, laboratory diagnostics. Medicine of extreme situations. 2019; 1: P.90-104.
2. Zharkova T.S., Kuznetsov S.V., Gubar S.O. The importance of inflammatory mediators in the formation of variants of the course of intestinal infection in children. Healthcare of Tajikistan. 2017; 1(332): P.15-20.
3. Ivanov, I.V. Hemocolitis syndrome in acute intestinal infections in children: clinical and laboratory features / I.V. Ivanov, O.S. Sidorova, G.M. Filippova, et al. // Bull. med. sciences. - 2017. N. 2 (6). P. 34 - 37.
4. Simbirtsev, A.S. Cytokines in laboratory diagnostics / A.S. Simbirtsev, A.A. Totolyan // Infectious diseases: news, opinions, training. - 2015. N. 2. P. 82-98
5. Chen ML., Sundrud MS. Cytokine networks and T-cell subsets in inflammatory bowel diseases. Inflammatory Bowel Diseases. 2016; 22(5):P.1157-1167.
6. Ince MN, Elliott DE. Immunologic and molecular mechanisms in inflammatory bowel disease. The Surgical Clinics of North America. 2017; 87(3):P.681-696.
7. Muzes G., Molnar B., Tulassay Z., Sipos F. Changes of the cytokine profile in inflammatory bowel diseases. World Journal of Gastroenterology. 2022;18(41):5848-5861. doi: 10.3748/wjg. v18.i41.5848.
