Vol 27, No 1 (2024)

Endogenous opioid system plays an important role in the regulation of body functions under stress, providing stress-protective, analgesic and immunoregulatory effects. The aim of this work was to assess the effect of acute cold stress on the in vivo production of adaptive immunity cytokines IL-2, IL-4, IFNγ, phagocytosis, and production of reactive oxygen species in non-immunized mice with induced blockage of opioid receptors. The object of the study were male white mice subjected to acute cold stress at -20 °C for 10 or 60 minutes. To block opioid receptors, naloxone hydrochloride was used, which was administered subcutaneously at a dose of 0.2 mg/kg 20 min before inducing the stress. After the cold exposure, spleen and peritoneal lavage were obtained from the animals. The cytokine concentrations were determined using ELISA technique. The absorption activity of CD11⁺ cells of the peritoneal cavity was assessed using FITC-stained St.cohnii with a flow cytometer; the production of reactive oxygen species was assessed using the reaction of luminol-dependent chemiluminescence.

It was found that the both cold stress regimens caused naloxone-independent inhibition of spontaneous IFNγ production. In stimulated cultures, an inhibitory effect on IFNγ secretion was registered in animals subjected to stress for only 60 min, being also independent on the opioid receptor blockade. IL-2 production decreased in stimulated cultures against the background of 60 min stress naloxone independently. Both variants of cold stress had no effect on IL-4 production. Stress for 60 min inhibited absorption activity of CD11⁺ cells from the peritoneal lavage and activated production of oxygen radicals, being, however, canceled by naloxone administration. Hence, acute cold stress led to naloxone-independent inhibition of Th1 cytokine production by splenocytes, naloxone-dependent inhibition of phagocytosis and activation of the microbicidal potential of peritoneal cavity cells.

Currently, a significant portion of the food consists of multiple different ingredients. Soybean proteins have been widely used for production of these combined foodstuffs. Meanwhile, soy proteins may contain a wide range of allergens, and even, if present in small amounts, they can cause severe allergic reactions due to cross-reactivity. The aims of our study were to evaluate the prevalence of sensitization to soybean allergen components Gly m 4, Gly m 5 and Gly m 6, and to map their IgE cross-reactivity with homologous proteins of Bet v1-like proteins and cupin proteins in patients with atopic disorders. We have studied IgE’s to 112 allergenic components of plant and animal origin in blood sera from 54 patients with history of allergy, using the ImmunoCap ISAC method. The results were analyzed by means of MS Excel program using parametric statistical criteria. Results: In patients with atopic diseases, we have detected serum IgE to the rGly m 4 allergic component (5 patients out of 29; 17.24%). Frequency of sIgE detection to rGly m 5 (3 patients of 29; 10.24%) and rGly m 6 (1 patient of 29; 3.44%) was less pronounced. Cross-reactive sIgE was detected only to allergens of the Bet v1 superfamily. The strongest relationship was found between sIgE level to rGly m 4 and rBet v1 (R = 0.68; p = 0.001). Another IgE cross-reaction was found between soybean rGly m 4 and alder pollen rAln g1 (R = 0.681; p = 0.000). IgE antibodies to rGly m 4 may also cross-react with kiwi rAct d8 (R = 0.59; p = 0.001). We have also found a weak correlation between sIgE to soybean rGly m 4 and two hazelnut rCor a1 isoforms: rCor a 1.01 (R = 0.42; p = 0.023), and rCor a 1.04 (R = 0.39; p = 0.036). The IgE cross-reactivity profile of the soy allergens revealed in this study is important for improvement of testing strategy for the presence of causally significant allergens. This finding will help to avoid the development of hidden cross-reactions that trigger both oral and respiratory allergic processes in subjects with allergic pathology. Moreover, this will enable administration of optimal diets and develop technologies for development of hypoallergenic food products.

According to the WHO data, the incidence of measles is now in the cyclic increase phase. The non-vaccinated subjects, like as persons who have previously received one or two doses of measles vaccine are involved in the epidemic process. The purpose of our study was to determine the immunological pattern in the groups of measles patients of different age in areas with high incidence of infection. To determine the immune response type in measles patients, qualitative and quantitative indices of IgM and IgG were used, detected by the following ELISA test-systems: VectoMeasles-IgM (JSC “Vector-Best”, Russia); Anti-Measles Viruses ELISA (IgG) and Avidity Anti-Measles Viruses ELISA IgG (Euroimmun, Germany). The serological study of 1893 patient allowed to determine the primary and secondary types of immune response. In 72.64% of the patients with primary immune response, the serum samples contained low-avidity IgG at a concentration of 0.45 (0.22- 0.74) IU/mL. In the group with a secondary immune response, high-avidity antibodies were detected at a concentration of 24.28 (21.59-27.4) IU/mL. The antibody levels in secondary type of response was 54-fold higher than IgG values in the first group (p < 0.05). In the group with primary immune response, the ratio of children (< 1 to 14 years) and adults (18 to 70 years old) was almost the same (49.6% and 47.56%). Appropriate values for children and adult cohorts with a secondary immune response were 2.12% and 96.53%, respectively (p < 0.05). Among 46 teenagers (15-17 years old), 84.8% responded with a primary immune response to the measles virus. Thus, in the area with high-incidence of measles among patients of different age, the primary-type immune response was determined in 72.64%, and secondary-type, in 27.36%. We have found that in the patients with a secondary type of immune response group, the proportion of children and teenagers was 27.8 times lower than among adults, thus indicating to high efficiency of vaccination in pediatric population. At the same time, the results of studies among measles patients with primary-type immune response, both children and adults, suggest some “gaps” in the vaccine prevention program.

A common pathogenetic mechanism of reproductive losses and congenital heart disease (CHD) is associated with immune inflammation in the “mother-embryo” system which affects differentiation and proliferation of cardiovascular progenitor cells. It is hypothesized that this link may be blocked by regulatory auto- and alloimmune antibodies to HLA-G and HLA-DR molecules. Moreover, these antibodies may be present at sufficient amounts in donor immunoglobulins, especially those obtained from the blood of multiparous women. Based on this suggestion, the aim of our study was to obtain enriched gamma globulin fraction from the blood of multiparous women and evaluate its functional effects towards HLA-DR and HLA-G molecules.

Isolation of the gammaglobulin fraction (GGF) from the blood plasma of multiparous women was performed using affinity chromatography in several sessions. Purity grade of the resulting protein was analyzed by immunoelectrophoresis, electrophoretic separation of the protein fraction of blood serum and electrophoresis in 4.12% polyacrylamide gel with the addition of SDS (PAGE electrophoresis). PAAG electrophoresis showed that this GGF did not differ from commercial therapeutic intravenous immunoglobulin (IVIG).

Assessment of the functional activity of GGF upon HLA-DR and HLA-G molecules was performed in the main group of women and their children with congenital heart disease (n = 38), and control group of women who gave birth to conditionally healthy children (n = 21). To determine the specificity of GGF with respect to HLA-G, HLA-DR molecules, as well as to compare its effect with autologous and allogeneic sera and IVIG, we developed an immunological testing protocol using flow cytometry. The protocol was arranged on the basis of the methodology of “cross-match” approach and Russian patent “Method for determining antibodies to HLA-G”. It was found that the blocking activity of female serum towards autologous (intrinsic) and allogeneic (embryo/fetus/child) HLA-G and HLA-DR molecules may determine the protective effect on development of congenital heart defects in the next generation. Donor human immunoglobulin showed a similar blocking effects to these molecules, possibly due to the presence of alloimmune antibodies to HLA classes I and II. The gammaglobulin fraction obtained from the donor blood of multiparous women has a more pronounced blocking effect on the HLA-G and HLA-DR expression. Hence, this immunobiological preparation can be considered a prototype of therapeutic and prophylactic agent blocking the genesis of congenital heart defects.

The present study concerns clinical effects of speleotherapy in bronchial asthma. The aim of our work was to study the efficiency of speleotherapy in a group of patients with bronchial asthma. We observed a group of 51 patients with bronchial asthma (BA) aged 18 to 50 years, who received a course of treatment at the private center “Solevik” (Yakutsk City), carried out at the Department of Allergology and Immunology. All the examined patients were diagnosed with atopic bronchial asthma, of moderate severity. Basic therapy in all cases included Symbicort and Seretide treatment. The patients were managed and monitored before and after the course of treatment by a therapist, pulmonologist and allergologist-immunologist at the outpatient center. Laboratory parameters included general blood tests and the levels of total serum IgE. Examination of patients after a course of speleotherapy revealed disappearance and reduction of asthma attacks (up to 1 attack per month) in 80% of the examined. General blood testing before and after speleotherapy showed decreased levels of blood eosinophils after the course of treatment. I.e., the average initial level of blood eosinophils before treatment was 12±0.4%, being decreased after the course of speleotherapy to 5.5±0.2%. Measurements of total IgE before and after speleotherapy revealed the following results: in patients before therapy, the average level of this index was 500±0.8 units/mL. After a course of speleotherapy, this parameter decreased to 80±0.3 units/ mL.

Speleotherapy shows a positive effect on the clinical course of the patients with bronchial asthma and significantly increases the efficiency of treatment.

Papillomavirus infections (PVI) are among the most common sexually transmitted diseases in the young population. A long, sluggish inflammatory process sufficiently worsens adequate preparation for normal pregnancy. Herpesvirus and Chlamydia infections are the most frequent associations with papillomavirus infection. Many authors believe that PVI may cause dysregulation of pro- and anti-inflammatory cytokines revealed in blood serum. Currently, there are no uniform standards for management and treatment of women with papillomavirus infection without pronounced clinical manifestations, in order to prevent morphofunctional disorders of genitourinary system leading to reproductive disorders. However, most authors believe that antiviral and immunomodulatory drugs are the main tool of therapy against expansion of pathogens in the body. The aim of our study was to compare changes in the levels of IL-17, IL-12 p70, IL-12 p40, IL-13 and TGF-p1 in blood serum of women with papillomavirus infection before and after therapy with Inosine pranobex (IP) and Solanum tuberosum (ST).

We conducted a survey of 137 patients with papillomavirus infection treated with drugs containing Inosine pranobex and Solanum tuberosum as active substances. The levels of IL-17, IL-12 p70, IL-12 p40, IL-13, and TGF-p1 in blood serum were determined using specific reagents from R&D Diagnostics Inc. (USA).

Changes in pro- and anti-inflammatory cytokines before therapy were as follows: decreased levels were found for IL-12 p70, p40; increased values were revealed for IL-13, IL-17, and TGF-p1. After the courses of therapy, we have registered the following changes in PVI-infected patients treated with synthetic drug Inosine pranobex (IP): the levels of IL-12 p70, IL-12 p40 were increased, along with decrease in IL-13 and TGF-p1. Meanwhile, ST therapy was associated with increase in IL-12 p70, IL-12 p40, and a decrease in IL-13 and TGF-p 1. With IP therapy, patients with combined HPV + HV infection showed an increase in IL-12 p70, IL-12 p40 and a decrease in IL-13, while TGF-p1 did not change. Following ST therapy, these patients exhibited higher IL-12 p70, IL-12 p40, decreased IL-13, whereas TGF-p 1 remained unchanged. In the group of women with HPV + Chlamydia infection, an increase in IL-12 p70, IL-12 p40 and a decrease in IL-13 and TGF-p1 was associated with IP therapy. An increase in IL-12 p70, IL-12 p40 and a decrease in IL-13 and TGF-p 1 were shown after ST therapy. In all groups of patients, IL-17 remained at high levels after therapy without significant differences between the mentioned subgroups. In the groups of patients treated with IP. we have recorded a general normalization of immune disorders.