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Vol 20, No 1 (2023)

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Reviews

The predicting value of circular DNA particles of T- and B-cell receptors for the dismal acute period outcomes and the disease severity of COVID-19 infection

Elistratova T.A., Tikhonova E.P., Savchenko A.A., Borisov A.G.

Abstract

The pandemic of the new coronavirus infection COVID-19, caused by the SARS-CoV-2 virus, continues to be a serious problem for the entire global community. Currently, most patients experience mild COVID-19, with only about 20% of those infected requiring hospitalization. The severe course of COVID-19 is most often associated with damage to the patient’s bronchopulmonary system by the virus and serious abnormalities, including damage to the air-hematological barrier, systemic inflammation, dysfunction of the immune system and the addition of secondary infections. Severe disease and poor outcome in hospitalized patients with COVID-19 may be associated with lymphopenia in combination with neutrophilia. Restoring the number of lymphocytes is important to improve the prognosis of the patient’s outcome. Patients with COVID-19 experience an immune imbalance where systemic inflammation and dysfunction of circulating T and B cells lead to more severe disease. TREC/KREC analysis can characterize the function of the central organs of the immune system and its relationship with clinical and laboratory data. Decreased TREC/KREC levels were observed in patients with unfavorable disease outcomes compared to patients with favorable disease outcomes. Additionally, a higher neutrophil to lymphocyte ratio was found. Levels of TREC and KREC in the blood negatively correlate with the neutrophil-lymphocyte ratio. Thus, the TREC/KREC assay is a potential prognostic marker for assessing the severity and outcome of COVID-19.

Cytokines and inflammation. 2023;20(1):5-12
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Original Study Article

Evaluation of the production of oppositional cytokines IL-6 and IL-10 in the culture of mononuclear blood leukocytes in rats with metabolic syndrome

Voronkova O.V., Birulina Y.G., Esimova I.Y., Khasanova R.R., Ivanov V.V., Buiko E.E., Chernyshov N.A.

Abstract

Aim: to evaluate the secretory activity of mononuclear blood leukocytes by the level of in vitro production of oppositional cytokines (pro-inflammatory IL-6 and anti-inflammatory IL-10) in rats in a model of diet-induced metabolic syndrome (MS) against the background of changes in the concentration of adipokines leptin and adiponectin.

Materials and methods. In male Wistar rats, MS was modeled by keeping for 12 weeks on a high-fat and high-carbohydrate diet; control group animals received a normal diet. Mononuclear leukocytes isolated by gradient centrifugation from heparinized blood were cultured in a medium based on RPMI-1640 (concentration of 2×106 cells in 1 ml of medium) for 24 hours in sterile tubes in a CO2-incubator in two variants – without the addition of an inducer and with the addition of bacterial lipopolysaccharide (LPS). The concentration of cytokines in the culture fluid, hormones leptin and adiponectin in the blood serum was determined by enzyme immunoassay. Statistical data processing was carried out in the SPSS Statistics 23.

Results. In animals exposed to a 12-week high-fat and high-carbohydrate diet, against the background of an increase in body weight, the specific mass of visceral adipose tissue, metabolic disorders (hyperglycemia, impaired glucose tolerance, dyslipidemia), high concentrations of leptin and low concentrations of adiponectin, the ability of mononuclear blood leukocytes to produce IL-6 and IL-10 in vitro at the basal level and when stimulated by bacterial LPS does not change.

Conclusion. Probably, the morphofunctional status and secretory profile of monocyte-macrophage system cells depends on the severity and duration of the metabolic and hormonal imbalance associated with obesity and systemic chronic inflammation.

Cytokines and inflammation. 2023;20(1):13-17
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Peculiarities of cytokine and chemokine content in blood serum of children with psoriasis vulgaris

Kuptsova D.G., Radygina T.V., Murashkin N.N., Freidlin E.V., Kurbatova O.V., Petrichuk S.V.

Abstract

Psoriasis is a chronic auto-inflammatory skin disease with a hereditary predisposition due to the activation of T-lymphocytes and the synthesis of pro-inflammatory cytokines. The pathogenesis involves populations of Th1 and Th17 lymphocytes that produce TNFa, IFNy, IL-17, IL-21 and IL-23. The aim of the study was to identify the features of the content of cytokines and chemokines in the blood serum of children with psoriasis. 88 children with psoriasis of varying severity were examined. The level of circulating cytokines was determined by the multiplex method on the Bio-plex 200 device using the MILLIPLEX MAP Human Th17 kit. In children with psoriasis, increased levels of IL-23, IL-22, IL-12p70, IL-27, IL-17E, IL-17F and TNFa were detected. The consistency of the functioning of the cytokine network in children with psoriasis was shown, which was expressed in the high strength of the connection between cytokines of the IL-17 family and cytokines of the IL-12 family, between IL-31 and IL-33, as well as in significant correlations between GM-CSF and cytokines IL-2, IL-5, IL-9, IL-10, IL-15 and TNFa. In children with psoriasis, the dependence of the level of IL-17A, TNFa, IL-2, IL-6, IL-9, CCL20/MIP3a with the severity of the disease according to PASI was revealed. The study confirmed the pathogenetic role of the cytokine network in the development and maintenance of an inflammatory response in children with psoriasis. The data obtained substantiate the need for targeted anti-cytokine therapy. The level of proinflammatory cytokines in children with psoriasis can be used as an additional laboratory criterion for the severity of the condition and monitoring the effectiveness of therapy.

Cytokines and inflammation. 2023;20(1):18-24
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Immunoregulatory properties of the dry extract of the herb Cichorium intybus L. in in vitro and in vivo systems

Mikhailova I.V., Ivanova E.V., Smolyagin A.I., Bondarenko A.I., Sinegovets A.A., Bondarenko T.A., Bekpergenova A.V.

Abstract

Aim: to evaluate the effect of a dry extract of the herb of Cichorium intybus L. on the production of cytokines by human peripheral mononuclear cells in the systems in vitro and on the mass (thymus, spleen) and number of cells (thymus, spleen, bone marrow) of immune organs of mice in a model experiment of immunodeficiency in the systems in vivo.

Materials and methods. The study of the immunoregulatory properties of the dry extract of chicory herb was evaluated by the ability to change the production of cytokines on the model of mononuclear cells during co-cultivation under in vitro conditions and by the ability to restore the mass (thymus, spleen) and the number of cells (thymus, spleen, bone marrow) of the organs of the immune system of outbred mice under conditions of immunosuppression induced by methotrexate to the level of intact mice in vivo.

Results. An analysis of the immunoregulatory properties of dry extract of chicory herb in the systems in vitro showed that a solution of chicory extract increased the concentration of the anti-inflammatory cytokine IL-10 and reduced the production of pro-inflammatory cytokines TNFα, IL-6, IFNγ and anti-inflammatory cytokine IL-1Ra. Evaluation of the effect of the dry extract of chicory herb in the systems in vivo found that the dry extract of the herb of Cichorium intybus L. had no effect on the mass (thymus, spleen) and number of cells (thymus, spleen, bone marrow) of the immune system organs in intact mice and restored these parameters of the immune system in animals treated with cytostatic MTX to the level of intact animals, and the effect of the extract was comparable to the effect of the reference drug “Immunal”.

Conclusion. The dry extract of the herb of Cichorium intybus L. can be considered as a promising agent that normalizes the parameters of the immune system under conditions of MTX-induced immunosuppression, suppresses the synthesis of pro-inflammatory cytokines and stimulates the secretion of anti-inflammatory IL-10, and the activity of this extract is associated with high content of phenolic compounds. Given the above, further study of chicory herb and dry extract from it is expedient and aimed at creating new effective herbal preparations that regulate the functions of the body’s immune system.

Cytokines and inflammation. 2023;20(1):25-31
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Promising directions in the development of new vaccines against papillomavirus infection

Nikitina T.N., Rayevskaya N.M., Solovieva I.L., Simbirtsev A.S., Volgin A.R.

Abstract

Papillomavirus infection is one of the most common viral infections worldwide. Highly oncogenic types of human papillomavirus (HPV) are the root cause of cancer of the cervix, vulva, vagina, genitals in men, anal cancer, as well as cancer of the oropharyngeal region. Currently, three HPV vaccines have been registered and successfully used in Russia: divalent (HPV types 16, 18) and quadrivalent (HPV types 6, 11, 16, 18). In the countries of America and Europe, a nine-valent vaccine is available, which contains nine types of HPV (6, 11, 16, 18, 31, 33, 45, 52, 58). These vaccines are preventive, have high immunogenicity and induce the production of specific antibodies. The action of preventive vaccines is aimed at creating specific humoral immunity to the capsid proteins of the virus, which leads to the prevention of HPV infection. Nevertheless, there are no specific medicines on the pharmaceutical market aimed at treating an already established pathology.

Currently, active development of HPV vaccines with both preventive and therapeutic effects is underway. Candidates of therapeutic HPV vaccines undergo various stages of research. Experimental vaccination systems on animal models provide encouraging results. If preventive and therapeutic HPV vaccines prove to be effective in patients as well as in animal models, then pillomavirus infection and related malignant diseases can be controlled by vaccination.

Cytokines and inflammation. 2023;20(1):32-40
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Characteristics of innate immunity cells after diseases caused by the SARS-COV-2 virus

Plekhova N.G., Prosekova E.V., Sitdikova T.A., Dubiy A.A., Mikhailov A.O.

Abstract

Hyperinflammation and dysfunction of the immune response during COVID-19 infection develops due to the reaction of innate immune cells to the introduction of the SARS-CoV-2 virus. The expression of receptors on these cells reflects the degree of their activation and makes it possible to assess the intensity of inflammation. The purpose of this study were to study the structural and functional features of innate immunity cells in patients. The specific gravity and absolute content of neutrophils (CD11b+, CD16+, CD18+) and monocytes (CD14+CD16, CD14CD16+, CD11b+, CD18+) in the peripheral blood of patients were determined. The contingent of the study included 60 people, of which: 47 had had a coronavirus infection COVID-19 (confirmed by PCR) in the 12 weeks preceding the study, and 13 had no history of it. In the peripheral blood of people who had COVID-19, compared with those who had not been ill, a significantly lower number of monocytes of the classical (CD14CD16+) and, on the contrary, a greater number of non-classical (CD14+CD16) cell populations were determined (p<0.05). Also in these individuals, a high proportion of monocytes carrying the adhesion receptors CD11b and CD18 (p<0.01) and a high content of neutrophils expressing the adhesion receptor CD11b+ and CD16+ (p<0.05) was noted. Thus, the results of a study of the expression of various types of receptors on monocytes and neutrophils illustrated the long-term preservation of aberrant structural and functional characteristics of innate immunity cells in individuals who underwent COVID-19.

Cytokines and inflammation. 2023;20(1):41-46
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Features of phagocytic and chemiluminescent activity of neutrophils when exposed to polyprenols in vitro

Savchenko A.A., Belenyuk V.D., Gvozdev I.I., Borisov A.G.

Abstract

Aim: Studying of the features of phagocytic activity and the state of the respiratory burst of neutrophils under the influence of polyprenols in vitro.

Materials and methods. The study involved 30 relatively healthy donors aged 23-59 years from whose peripheral blood neutrophilic granulocytes were isolated to determine phagocytic and chemiluminescent activity. The isolated cells were incubated for 30 minutes with polyprenols in vitro. The level of phagocytosis of immature and mature neutrophils was determined by flow cytometry using FITC-labeled staphylococcal protein A. The state of the respiratory burst was assessed using chemiluminescent analysis.

Results. It was found that the levels of phagocytic index (PI) and number (PN) of mature neutrophils were reduced after incubation with polyprenols relative to initial and control values. The values of PI and PN of immature neutrophils under the influence of polyprenols and during control incubation were decreased relative to the initial values. The intensity maximum and area under the curve of spontaneous and zymosan-induced lucigenin- and luminol-dependent chemiluminescence of the neutrophils were reduced after incubation with polyprenols.

Conclusion. The effect of polyprenols on neutrophilic granulocytes in vitro leads to a decrease in activity in respiratory burst cells, which is realized in blocking by polyprenols the interaction of primary and secondary ROS with chemiluminescent indicators by the mechanism of primary antioxidants. The binding of ROS by polyprenols also manifests itself in a decrease in the phagocytic activity of mature neutrophils while maintaining the phagocytic activity of immature cells at the level of control incubation. In general, polyprenols exhibit anti-inflammatory activity when exposed in vitro to neutrophilic granulocytes.

Cytokines and inflammation. 2023;20(1):47-53
pages 47-53 views

Features of the respiratory burst state of neutrophils and the activity of NAD(P)-dependent dehydrogenases in patients with widespread purulent peritonitis in the prognosis of the development of sepsis

Savchenko A.A., Borisov A.G., Gvozdev I.I.

Abstract

Aim: Studying of the respiratory burst state and NAD(P)-dependent dehydrogenases activities in blood neutrophils features in the forecast of the development of abdominal sepsis in patients with widespread purulent peritonitis (WPP).

Materials and methods. The study involved 50 patients with WPP in the preoperative period. Abdominal sepsis was developed by 35 patients (70.0%) from 5 to 10 days postoperative period, 15 patients (30.0%) hadn’t complications. The respiratory burst condition of blood neutrophils was examined using a chemiluminescent assay. Intracellular activity of the NAD- and NADP-dependent dehydrogenases was researched with using bioluminescent methods.

Results. It was found that patients with WPP whose dynamics of the preoperative period will develop sepsis the chemiluminescent activity of blood neutrophils was characterized by a reduced level of spontaneous synthesis of the primary reactive oxygen species (ROS) and elevated levels of spontaneous synthesis of secondary ROS relative of the indicators identified in patients without subsequent complications. The feature of neutrophil metabolism in WPP patients without subsequent development of sepsis was high activity of the anaerobic lactate dehydrogenase reaction and decrease in activity of the NADP-dependent decarboxylating malate dehydrogenase. In patients with WPP and the subsequent development of sepsis was found high level of NAD-dependent substrates outflow citric acid cycle in the reaction of amino acid metabolism via glutamate dehydrogenase that may affect the activity of aerobic respiration in the neutrophils. Using correlation analysis was found that the intensity of the neutrophils respiratory burst in patients with no subsequent complications depends on the activity of anaerobic glycolysis.

Conclusion. The established differences in the state of the respiratory burst and the activity of enzymes in neutrophils in patients with WPP, in depending on the subsequent development of the sepsis, determine the possibility of developing the method of forecasting complications and developing immunoactive therapy in the postoperative period of WPP. 

Cytokines and inflammation. 2023;20(1):54-62
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The effect of post-covid syndrome on the cytokine cascade in patients with type 2 diabetes mellitus

Savchuk K.S., Simbirtsev A.S., Ryabova L.V.

Abstract

With the increasing prevalence of type 2 diabetes, it is of interest to study the characteristics of the immunological status in this category of patients. According to modern data, in type 2 diabetes, a pro-inflammatory type of immune response is formed with an imbalance between T-helper 1 (Th1), T-helper 2 (Th2), T-helper 17 (Th17) types and T-regulatory cells (Treg). The COVID-19 pandemic makes a certain contribution to changes in the immune response in patients with type 2 diabetes mellitus, since in patients who have had coronavirus infection, significant changes in the composition of circulating immune cells are observed: the proportion of Th17 increases and the number of Tregs decreases. This study is devoted to identifying the features of the cytokine cascade in patients with type 2 diabetes mellitus, depending on the presence of a confirmed history of SARS-CoV-2 infection. The study included 75 patients with type 2 diabetes, in 36 of them the diagnosis was verified in the post-Covid period. The study was conducted at least 6 months after pneumonia caused by SARS-CoV-2 infection. All study participants signed informed consent. The study was approved by the Independent Local Ethics Committee at the State Autonomous Institution of Regional Clinical Hospital “City Clinical Hospital No. 1” of Chelyabinsk, protocol No. 8 dated 04/11/2022, on the basis of which these studies were conducted. Using the multiplex assessment method, the concentrations of 15 cytokines in the blood serum were assessed in patients: GM-CSF, IFNγ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17A, MIP-1β, TNFα. The results obtained during the study showed not only a change in the number of cytokines, but also a change in the balance of pro- and anti-inflammatory cytokines, cytokines that regulate forms of development of acquired immunity, in the group of patients with type 2 diabetes in the post-Covid period. In the post-Covid period, in patients with type 2 diabetes mellitus, the concentrations of cytokines secreted by Th1, Th2, Th17 cells, and Tregs sharply decreased. It has been determined that patients with type 2 diabetes mellitus after SARS-CoV-2 infection develop a functionally inferior virus-specific T-cell response, characterized by reduced or suppressed secretion of the cytokines GM-CSF, IFNγ, IL-1β, IL-2, IL -4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 (p70), IL-13, IL-17A, MIP-1β, TNFα. A weak T-cell response may increase the likelihood of developing pathological processes associated with an inadequate response to viral antigens (including repeated infections with the SARSCoV-2 virus, exacerbation of chronic infections).

Cytokines and inflammation. 2023;20(1):63-66
pages 63-66 views

Non-specific prevention of respiratory infections during vaccination against COVID-19

Khasanova A.A., Soloveva I.L., Kostinov M.P., Nikitina T.N., Ganina E.S., Nastaeva N.Y., Krukova N.O., Korovkin S.A., Baranova I.A.

Abstract

The novel coronavirus infection (COVID-19) has a suppressive effect on innate immunity, which is a prerequisite for developing strategies to enhance this non-specific link as a preventive measure to protect against other respiratory infections during the ongoing circulation of mutating strains of the SARS-CoV-2 virus. Despite the currently developed and available preventive measures, it has been noted that in persons who have undergone COVID-19, repeated episodes of both coronavirus infection and diseases caused by other pathogens have been recorded.

This review analyzes data from the biomedical literature and considers examples of health risks associated with continued infection with pathogens that cause respiratory tract pathologies. It also reflects the ways and approaches of possible preventive measures, the purpose of which is to prevent the development of pathologies of both the respiratory organs and other systems.

Cytokines and inflammation. 2023;20(1):67-76
pages 67-76 views

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