Current issue
3 . 2019
Сytokines

Modifi cating impact of semax on interleukin-1β level under stressinduced conditions

Abstract

This study is devoted to an experimental study of the effect of semax (Met-Glu-His-Phe-Pro-Gly-Pro) on the level of interleukin-1β under the conditions of informational, «social» and immune types of stress. Informational stress was modeled by shaping food-producing behavior in a multi-alternative maze. As a model of «social» stress, a model of sensory contact was chosen. Immune stress was modeled by a single intraperitoneal injection of a lipopolysaccharide isolated from Salmonella typhi microbial cells. The level of serum interleukin-1β was determined by the method of enzyme-linked immunosorbent assay. «Social», informational and immune types of stress, formed in our experiment, are accompanied by increased production of interleukin-1β, which allows us to consider stress, regardless of its type, severity and duration, as an inducer of cytokine production of the pro-inflammatory interleukin family. Evaluation of the effect of semax on the level of IL-1β under stress-induced conditions has shown that this neuropeptide causes suppression of the production of interleukin, accompanied by a decrease in its level.

Oncoimmunology

Features of peripheral blood lymphocytes and tumor infiltrating lymphocytes subpopulations in patients with squamous cell head and neck cancer

Abstract

The immune system plays an important role in the development, formation and progression of squamous cell carcinoma of the head and neck. Therefore, the study of the baseline state of systemic and local immunity and of the link of lymphocyte subpopulation composition with prevalence of the process and survival of patients is relevant.

Material and methods. Immunophenotyping of peripheral blood lymphocytes (PB) and lymphocytes infiltrating the tumor (TILs) by flow cytometry was carried out in 29 primary operable patients suffering squamous cell carcinoma of the head and neck prior to surgical treatment.

Results. In patients with early stages of disease there was an increase in the percentage of NK-cells, CD16+Perforin+- and CD11b+-lymphocytes, as well as cytotoxic potential of CD8+-cells. The number of activated CD25+-lymphocytes was increased in patients with stages III-IV and the ratio of the Teff/Treg was decreased versus group of comparison. The percentage of regulatory CD4+CD25+CD127-/low-T-cells (Treg) was increased and the value of the Teff/Treg ratio was reduced in dead patients in contrast with survivors. Cytotoxic potential of CD8+-cells and CD8+Perforinhigh-lymphocytes was elevated in living patients. The composition of TILs showed a significant increase of suppressor CD4+- and CD8+-T-cell populations compared with PB. There was also an increase in the percentage of CD8+- and CD4+-T-cells expressing the inhibitory receptor PD-1 compared with PB, and a high expression PD-L1 and PD-L2 on tumor cells.

Conclusion. Results indicate that simultaneous study of immune cells of peripheral blood and cells infiltrating tumor tissue is necessary.

The subpopulation balance of effector cells in the peripheral blood of cancer patients

Abstract

Effector cells (EC) of the immune system recognize and destroy tumor cells continuously formed in the human body, realizing the function of immune surveillance. Changes in the ratio between populations of effector cells may have prognostic value in the treatment of tumor diseases.

Material and methods. Peripheral blood lymphocytes were analyzed by flow cytometry. The study included 389 patients: primary resectable ovarian cancer (OC) - 91, cancer of the mucous membrane of the oral cavity - 72, breast cancer (BC) - 144, metastatic melanoma - 82 and 64 donors.

Results. It was shown that cytotoxic T lymphocytes (CTL) are the main population of cancer patients with EC, except for ovarian cancer, where NK-cells predominate. We identified a broad range of the content of CD8+-lymphocytes of cancer patients, and most patients had a high number of EC. We described the features of the subpopulation balance of EC that are specific to certain nosological forms of malignant diseases. For patients with ovarian cancer, breast cancer and oral mucosa cancer, it was noted that the decrease in CD8+-cells is accompanied by a decrease in the number of CTL and NKT cells and an increase in the proportion of NK lymphocytes in the structure of the effector link of immunity. In patients with melanoma, CTL remains the main population of EC and with a small number of CD8+-lymphocytes.

Conclusion. Phenotypic characteristics of cells of adaptive and innate immunity, their subpopulation structure, vary greatly in cancer patients. Data on the subpopulation structure of the effector immunity of patients can be used for correction and personalization of the therapy.

Clinical immunology

Sex and age differences of the systemic inflammatory response in experimental endotoxinemia

Abstract

The morphological and functional state of the integrative systems of the organism - endocrine, immune and nervous, in humans and animals, as well as susceptibility to diseases and the severity of their course are determined mainly by the karyotype and the content of sex steroid hormones, the concentration of which varies in individuals of different sex and age. The study evaluated differences in the systemic inflammatory response and morphological changes in the liver and lungs during experimental endotoxinemia induced by the injection of 15 mg/kg lipopolysaccharide (LPS) of E. coli in females and males Wistar rats of three age groups: newborns (2 days old), prepubertal (10 days old) and sexually mature (2-3 month old). In a day after LPS injection the severity of the inflammation was estimated by the number of neutrophils in the interalveolar septa of the lung, liver necrosis area, the activity level of liver enzymes - ALT and AST, endotoxin level, and the concentration of C-reactive protein in the blood serum. Concentration of corticosterone, estradiol and testosterone in the blood serum by ELISA. It was shown that, compared with newborn and adult Wistar rats, the most severe course of LPS-induced inflammatory response is observed in the prepubertal females and males, which are characterized by low serum concentrations of estradiol and testosterone. Despite the absence of sex differences in the concentration of steroid sex hormones in rats of the prepubertal period, the severity of the systemic inflammatory response in prepubertal males was higher than in females, as evidence by more pronounced inflammatory and pathological changes in the lung and liver, the increase of C-reactive protein in the serum. As in the prepubertal period, the severity of the inflammatory response in newborn and adult rats is more pronounced in males, which is apparently due to the genotype. The obtained data can serve as a basis for the development of new approaches to the effective personalized treatment of infectious and inflammatory diseases considering age and sex.

Methods

Theoretical and experimental rationale of the selection of promising methods for quantitative determinationof immunoglobulins G, A and M in human immunoglobululin products

Abstract

The selection of advantageous methods and experimental substantiation of their suitability for quantitative determination of immunoglobulin A impurity and/or for studying the composition of the main active ingredient in normal human immunoglobulins [IgG + IgM + IgA] is a pressing challenge brought about by the need to improve the quality of these products. The aim of the study is theoretical and experimental justification of the selection of promising analytical techniques using immunochemical reagent kits for determination of immunoglobulins A, M and G content in human immunoglobulin products.

Materials. Human immunoglobulin samples for intravenous administration with a known content of immunoglobulins belonging to specific classes. The paper presents the results of assessment of accuracy, repeatability, and intermediate precision of Kinetic nephelometry, ELISA and Mancini radial immunodiffusion method using available commercial immunochemical reagent kits. The paper substantiates suitability and promising outlook of these analytical methods for quantitative determination of immunoglobulins G, A and M in human immunoglobulin products. It was concluded by the authors that reliable results, independent of the chosen method and immunochemical reagent kit, can only be obtained if the test sample was studied using reference standards (showing properties and/or composition of the main active ingredient) calibrated against the international reference standard.

The problems concerned with undesirable immunogenicity of biotechnological medicines (therapeutic proteins). Part 1. Methodological approaches to the evaluation of immunogenicity

Abstract

The review provides information on issues related to the manifestation of unwanted immunogenicity of biotechnological drugs (therapeutic proteins) intended for the treatment of severe chronic diseases. The information on factors that affect the immunogenicity of the drug, including its structural and physico-chemical characteristics, as well as disease-mediated and dependent on the patient is provided. Provides general information about the clinical manifestations of the immune response to the medicines, the principles of studying immunogenicity and assessment of the risks connected with the clinical consequences of manifestation of «unwanted» immunogenicity of therapeutic proteins. Methodological approaches to the study of the immune response induced by the administration of the medicines are presented.

Reviews

Immunostimulators of muramylpeptide nature in the treatment and prevention of infectious-infl ammatory processes

Abstract

With the introduction of a pathogenic microbe, the development of an infectious disease largely depends on the innate immunity of the entrance gate of the infection, which in most cases are the mucous membranes of the respiratory, gastrointestinal and Uro-genital tract. Not only classical cells of the immune system, but also epithelial cells of the mucous membranes take part in the creation of anti-infectious protection of the mucous membranes. Therefore, the immunostimulating effect of drugs should be directed not only to the cells of the immune system, but also to the barrier epithelial layer, which will quickly and effectively eliminate the pathogen. The ability to stimulate both immune and non-immune component of anti-infectious protection have muramilpeptide preparations of nature and, above all, Lycopid®, which has shown high efficiency in the treatment and prevention of a number of diseases, including respiratory infections.

The immune system status of humans and animals during exercises of various origin

Abstract

Physical activity has a significant impact on the immune system of humans and animals. It should be noted that to date, the mechanisms of this impact have not been fully studied, and the available data are contradictory. In this review, the authors tried to systematize the results of studies on the characteristics of physiological and genetic features of the functioning of the key components of the immune system under physical stress of different Genesis and intensity. The qualitative and quantitative parameters of adaptive and innate immune response are described, as well as the main modern theories explaining the observed changes are considered. The review examines the effect of reduced physical activity in various models with hypokinesia, including real comic flight, where hypodynamic effects are clearly observed, and also considers the role of physical activity as a system for preventing the action of extreme factors in orbital space flights.

Innate lymphoid cells of human endometrium and decidua

Abstract

At present, several groups of innate immunity lymphocytes are described in the literature, among which are NK-cells, ILC (innate lymphoid cells) 1, ILC2, ILC3, and lymphoid inducer cells (LTi). The increasing evidence of ILC in various tissues suggests the presence of ILC in the uteroplacental complex, including the endometrium and decidual membrane. The purpose of the review was to analyze information about lymphocytes of the innate immunity of the endometrium and decidual membrane in humans. The review presents data on the population of NK cells of the endometrium, discusses possible ways of forming a pool of NK cells in the uterus. The text provides information about receptors and cytokines secreted by endometrial ILC2 and ILC3 cells. The phenotype of decidual NK cells was examined, the characteristics of the ILC1, ILC2, ILC3 populations and their possible functions were described. The analysis of the literature allows us to make a conclusion about the presence of virtually all populations of lymphocytes of innate immunity in the uterus and the participation of these cells in the physiological development of pregnancy. The increased number of distinct ILC populations in some cases and the marked changes in their secretory profile depending on the microenvironment indicate the possible contribution of individual ILC populations to the development of pregnancy pathologies.

Sepsis-induced immunosuppression

Abstract

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. In the former times the research was focused primarily on the immune hyperactivation, however sepsis-induced immunosuppression is now a widely recognized phenomenon. The main reasons of sepsis-induced immunosuppression are the dysregulation of apoptosis and autophagy, increased pro-inflammatory cytokines secretion, endotoxin tolerance phenomenon. At the moment there are a lot of biomarkers which can predict immunosuppression and incidence of secondary infections with different degree of certainty. In patients with the late phase of sepsis and immunoparalysis different immunostimulating agents, such as granulocyte-macrophage stimulating factor, interleukin 7, PD-1 and its ligand inhibitors, could be of a great value. The positive effect of these agents has been demonstrated in case series studies, currently randomized clinical studies are ongoing. Medications used in critical care have different effects on immunity. From our prospective, investigation of immunomodulating properties of antibiotics is of utmost importance. The existence of various effects of antibiotics on immune system is known for a long time, however, the current evidence is scarce and doesn’t allow us to make a judgement regarding the effects of the selected antimicrobic agent on the immunity. Understanding the influence of antimicrobials on immune system would guide our therapy taking into account not only on the infectious agent but also on the immune status of the host. We believe it is a critical matter in the light of growing antimicrobial resistance.

Obituary

Sergey Alexandrovich KETLINSKY (1940–2019)

Abstract

All articles in our journal are distributed under the Creative Commons Attribution 4.0 International License (CC BY 4.0 license)


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