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Study of the cytokine status in acute intestinal infections in children and its correction
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DOI: http://dx.doi.org/10.20534/ELBLS-16-4-43-45
Guliyeva Sevda Vagif, Halilov Vidadi Geidar, Research and Development Center, Azerbaijan Medical University E-mail: sevda.quliyeva.1970@mail.ru
Study of the cytokine status in acute intestinal infections in
children and its correction
Abstract: This work presents the results of examination of 136 children with acute intestinal infection (shigellosis, salmonellosis, proteus) of different etiology aged from 6 months to 3 years. Immune correction with a transfer factor immune modulator, compared to generally accepted therapy, was performed. It was revealed that the use of transfer factor immune modulator in the therapy of AII contributes to significant reduction of the level of cytokines in blood serum, i. e. stronger development ofproper and stable immunity than in the treatment with unaccepted therapy.
Keywords: IL6, IL18, transfer factor immune modulator, salmonellosis, proteus, shigellosis.
Introduction. High level of occurrence of acute in- mechanism of invasion is typical for shigella, salmonella,
testinal infections (AII) caused by salmonellosis, shigellosis as well as opportunistic pathogenic microflora, and difficulties in diagnostics and performance of rational therapy in patients determine the relevancy of the given problem (1, 2, 3). The issues of the pathogenesis of salmonellosis and other AII are actively studied in both, experimental and clinical trials. However, the results are controversial, often conflicting. Especially, when it is about cytokine response due to its multi-functionality and its relation to the clinical manifestation of AII in children depending on the age, sex, period and severity of the disease. In AII, immune system, which undergoes constant and intensive effect of various products of microbe life activity, including those referred to the factors of pathogenicity, is activated. The study of effector properties of cytokines led to the discovery of their role in the mechanism of receptor-mediated regulation of anti-infective protection of the organism (4). In the phase of acute inflammation, cytokines define the development of protective reactions at both, local level, in the zone of invasion of pathogen and the system level. The
as result of which inflammatory reaction is developed. Herewith, the death of epithelial cells takes place and clinical manifestations include fever, spastic contractions of the bowel, stomach pains, presence of mucus and/or blood in the motions. The components of bacterial cell wall such as lipopolysaccharides, toxins, peptidogly-cans etc., which initiate the production of interleukins (IL1, IL6, IL8) and tumor necrosis factor (TNF-a) play an important role in the initiation of cytokine synthesis at the initial stage of infection process. In turn, these cytokines contribute to the synthesis and secretion of the protein group called reactants of the acute phase of inflammation as well as other cytokines, which defines the cascade mechanism of cytokine production and variety of their biological effects (5). In AII caused by obligate-pathogenic triggers, the increase of concentration of antiinflammatory cytokines and proteins of the acute phase of inflammation takes place at relatively insignificant activation of specific immune mechanisms. This enhances the role of inflammatory proteins and cytokines in antimicrobe protection, not excluding the possibility of their
Section 2. Biomedical science
direct binding with the components of pathogen for in-activation and clearance from the organism.
Trials conducted earlier showed that dysbacteriosis developed during AII aggravates their course, contributes to the chronization of the process and formation of persistent diarrhea, reduces the efficiency of the effect of generally accepted therapy. It became obvious that the disruption of the functioning of immune system is one of the major factors affecting the development of AII, and the attempts to solve the problem with antibiotics and other etiotropic agents cannot ensure complete success (6). In this respect, the study of new ways of AII treatment, search of new schemes of treatment is an apparent task of modern medicine.
Goal of the research is to characterize the dynamics of the level IL-6, IL-18 in children with AII and perform immune correction with transfer factor immune modulator compared to generally accepted basis therapy.
Methods of the research. 136 children with AII of different etiology aged from 6 months to 3 years were examined. The children were divided into 2 groups. Group I received transfer factor immune modulator against the background of complex treatment. Group II received only generally accepted therapy. The control group included 10 healthy children of same age. Each group was subdivided into 3 sub-groups of patients: a) shigellosis; b) salmonellosis; c) proteus.
Simultaneously, the patients of sub-group I received immune correction. And the patients of subgroup II didn't receive immune correction. The levels of IL-6 and IL-18 in the blood serum were defined by the method of enzyme-linked immunosorbent assay (ELISA) with the assay kit by CJSC «Vektor-Best» on the device MS-500 with the following concentration range: IL6 5.6-300 pg/ml, IL18 0-1000 pg/ml. The statistical processing of results was conducted with the help of computer program «Statistika».
Results and discussion. The definition of fluctuations of the levels of cytokines in the dynamics of AII incidence caused by shigella and salmonella, as well as opportunistic flora (proteus) revealed that during the period of height of the disease, the level of IL-6 in different sub-groups exceeded the indicator in healthy persons (19-23 pg/ml). In the sub-group of the patients with shigellosis, the value reached 42-46 pg/ml (2,1 times higher); in the sub-group of children with salmonellosis, the value was 35-42 pg/ml (1,8 times higher); and in the sub-group of patients with opportunistic enteric bacterium proteus, the level of IL-6 was 1,5 times higher and accounted for 24-38 pg/ml.
In children with AII, the level of IL-18 in blood was defined and the increase of the level of cytokine by 2 times at the height of infection (see Table 1) was revealed. It was shown that in the blood of patients with the infections caused by shigella, the level of IL-18 was 2,5 times higher compared with the control group, and accounted for 370-430 pg/ml. In the blood of the patients with salmonellosis, this value was 1,3 times higher (280-380 pg/ml), and in the blood of the patients with the infection caused by opportunistic enteric bacterium proteus, the level of IL-18 reached 220-350 pg/ml, which exceed the control value by 1,1 times.
As result of treatment of the patients with AII with transfer factor immune modulator compared with generally accepted therapy, a significantly more expressed reduction of the level of anti-inflammatory cytokine IL-6 and anti-inflammatory interleukin IL-18 was noted (Table 1).
Herewith, the level of IL-6 in the treatment with immune modulator of AII patients caused by shigella, salmonella and proteus reduced by 1,5; 1.4; 1,5 times respectively (higher than in the treatment with generally accepted methods). The level of IL-18 in the sub-group of the patients with shigellosis reduced by 1.3; in the subgroup of the patients with salmonellosis — by 1.2; in the sub-group of the patients with proteus — 1.1 times. Table 1 shows that the level of IL-6 and IL-18 reduced insignificantly in generally accepted therapy.
This positive dynamics of laboratory indicators was accompanied by quicker improvement of general condition of the patients.
The obtained data contradicts the results of the research by Z. G. Tagirova and others (4), who also made a conclusion about the misbalance of the immune system with the increase of the severity of pathological process.
The use of transfer factor immune modulator in the therapy of AII of different etiology contributed to a more significant reduction of the level of cytokines in blood serum. Its use causes a quicker stopping of the disease and disappearance of all pathological manifestations.
According to the result of our research, one can say that the implementation of transfer factor immune modulator in children with AII leads to normalization of the levels of cytokines, i. e. stronger development of proper and stable immunity compared with generally accepted therapy. The response reaction of the organism to the implementation of this agent enhances.
It is known that membranous pathology contributing to high adhesion ofpathogenic flora and beginning of infectious process often takes place against the background of instability of cytomembranes and enhancement of in-
Influence of donaxine on physical and psychoemotional state of white mice at single and prolonged administration
tracellular free-radical processes. It is know from spe- modulator also has antioxidant and membrane-stabilizing cialized literature sources that transfer factor immune properties (7).
Table № 1. - Effect of transfer factor immune modulator on the level of IL-6 and IL-18 in children with AII of different etiology
Research group Control grouP Pg/ml Before treatment After treatment
Shigellosis Salmonellosis Proteus General y accepted therapy Immune modulator transfer factor
Shigellosis Salmonellosis Proteus Shigellosis Salmonellosis Proteus
IL-6 19-23 42-46 35-42 24-38 42-45 29-34 25-29 29-34 24-30 21-24
IL-18 240-280 370-430 280-380 220-350 376-413 326-418 287-342 289-319 240-370 250-280
Thus, apparently, the agent used by us to treat children with AII has a mediated effect throughout the infectious process having immune modulating effect on the way of development of cytokines and anti-bodies and anti-oxidant properties.
Significant increase of the level of pro- and anti-inflammatory cytokines at the beginning of the disease in children with AII as well as reduction of their concentration during the use of transfer factor immune modulator allow speaking about the efficiency of its use in AII.
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DOI: http://dx.doi.org/10.20534/ELBLS-16-4-45-48
Mirzaev Yuriy Rahmanovich, Candidate of Medical Sciences, Senior Scientific Researcher of Department of Pharmacology and Toxicology of Institute of Chemistry of Plant Substances, Academy of Sciences of Republic of Uzbekistan, Tashkent,
E-mail: rahmanych@rambler.ru Sanoev Zafar Isomiddinovich, Senior Scientific Researcher of Department of Pharmacology and Toxicology of Institute of Chemistry of Plant Substances, Academy of Sciences
of Republic of Uzbekistan, Tashkent, E-mail: ZafarSano19@mail.ru
Influence of donaxine on physical and psychoemotional state of white mice at single and prolonged administration
Abstract: As single, so prolonged administration of alkaloid donaxine, revealing aphrodisiac activity, in doses 3, 10 and 50 mg/kg per os have call positive changes on physical and psychoemotional state ofwhite mice.
