Vol 29, No 1 (2026)

The review presents the history of evolving views about interrelations between the immune, nervous, and endocrine systems, A number of arguments justify the concept suggesting that they are components of a single regulatory system, since their structures are tightly integrated into each other, and they use similar biologically active substances as signaling molecules. At the same time, distinct molecules, depending on the cell of origin, may be classified as neurotransmitters, hormones, or cytokines. Receptors for cytokines were found on peripheral neurons and vagal nerve endings, e.g., IL-4 regulates synaptic transmission. The ability of immune cells to produce hormones and neuropeptides has been recently proven. Catecholamines may originate from the cells of immune system. Hypothalamic neurosecretory cells express IL-1, and astrocytic glial cells may express interferon. They always act together, in functional regulation by complementing or replacing each other, having a common coordination center. E.g., the anterior lobe of pituitary gland, by secreting growth hormone, may affect synthesis and secretion of thymulin by epithelial thymic cells. Thus, the hypothalamic-pituitary-thymic axis is formed. On this basis, neuroimmunoendocrinology, a new scientific discipline, has emerged. The disorder of a distinct subsystem leads to significant changes in its other compartments. There is not a single type of pathology that would not involve all three components of the whole system. The unity of all components of the system is most clearly observed in stress, traumatic shock, and cytokine storm. Cross-usage of drugs for the therapy of diseases affecting either of the three systems is of particular interest. For example, usage of immunotropic drugs has found applications in the treatment of psychiatric disorders. Pharmacological effects on macrophages are currently implemented in the treatment of endocrine disorders. Thus, sufficient evidence has been accumulated to consider the immune, nervous and endocrine systems an integrated system of physiological regulation which is presumably based on transmission and processing of information.

Schnitzler’s syndrome is a rare but usually underdiagnosed autoinflammatory disease, characterized by monoclonal IgM gammopathy, persistent urticaria, intermittent fever, bone pain, and arthralgia or arthritis. Although first reported by Dr. Liliane Schnitzler in 1972, the syndrome continues to pose challenges in diagnosis, and it usually takes more than five years before it is properly identified. Disorders show up in a form of urticaria, arthritis, organomegaly, fever, lymphadenopathy, high ESR, leukocytosis, and bone pain. Central to its pathogenesis are immunologic perturbations and activation of the inflammasome. It is typically diagnosed through clinical exam with history and important feature identification such as monoclonal gammopathy and acute or relapsing urticarial rash. Therapeutically synthetic agents include anakinra, canakinumab, rilonacept, and anti-IL-6 have been used with variable success. Recent research also demonstrated how natural treatments such as Terminalia chebula, Emblica offcinalis, Schinus terebinthifolia, tulsi, asafoetida, and Wedelia plants have the potential for controlling the symptoms and changing inflammatory paths. Promising medicinal possibilities for these plants, according to in silico investigations, point to further research into their clinical uses. With new therapy paths that promise better patient outcomes, Schnitzler’s illness is overall a therapeutic challenge.

Accurate diagnosis and classification of leukemia are essential for effective treatment planning. Traditional cytochemistry relies on enzyme-based staining for morphological evaluation, while flow cytometry (FCM) employs monoclonal antibodies to detect multiple surface and intracellular markers. This systematic review and meta-analysis compared the diagnostic accuracy of cytochemistry and FCM in leukemia immunophenotyping. A systematic search of PubMed and Google Scholar was conducted according to PRISMA guidelines. Studies evaluating sensitivity, specificity, and accuracy of cytochemistry and FCM in diagnosing acute and chronic leukemia were included. Data extraction covered study characteristics, diagnostic markers, and performance outcomes. Meta-analysis was performed to compare diagnostic values across methods. Eleven eligible studies comprising pediatric and adult leukemia cases were analyzed. Cytochemical stains such as myeloperoxidase (MPO) and sudan black B showed high specificity (91-100%) and moderate-to-high sensitivity (60-97%), while periodic acid–Schiff (PAS) and nonspecific esterase had lower reliability. FCM demonstrated superior diagnostic performance with average sensitivity of 87.7% and specificity of 85.6%, achieving > 95% accuracy in several studies. Marker panels including CD3, CD45, CD79a, and MPO enabled precise subtype differentiation and minimal residual disease detection. Cytochemistry remains useful as an affordable screening tool in resource-limited settings, but FCM provides greater sensitivity, specificity, and comprehensive immunophenotypic data, making it the preferred method for leukemia diagnosis and monitoring. Combining both approaches can enhance diagnostic performance across diverse clinical contexts.

Reactive erythemas represent a group of dermatoses with complex immunogenesis, in which γδ T cell subpopulations may be involved, like as in development of many autoinflammatory diseases. Despite an important role of IL-17, its excessive synthesis, e.g., by γδT cells, is able of inducing autoinflammation. On the contrary, IL-10 plays a key role in the control of innate immune responses. It may suppress functions of monocytes/macrophages by reducing pro-inflammatory cytokine production. Our aim was to perform in vitro expansion of γδ T cells by culturing lymphocytes from peripheral blood of patients with erythema. Peripheral blood mononuclear cells (PBMC) were isolated from 8 patients with reactive erythema (5 patients with erythema multiforme, 1 patient with ring–shaped centrifugal erythema, 2 patients with erythema migrans, an early form of Lyme disease), and two healthy donors aged 23 to 70 years. A modified van Acker et al. method (2016) was used to culture γδ T lymphocytes. The blood cell cultures were supplied with zoledronate, IL-2 and IL-15. The contents of IL-17 and IL-10 were determined in cell culture supernatants by solid-phase ELISA using Human IL-17 ELISA Kit (RK00397, ABclonal Biotechnology Co., China) and Interleukin- 10-ELISA-BEST (JSC "Vector-Best", Russia) according to the manufacturers’ instructions. In patients with reactive erythema, 3.1% to 62.8% of cells with expression of γδ TCR were obtained by 7 days of cultivation with zoledronate, IL-2 and IL-15. The lowest percentage of these cells was observed in blood cell culture from patients with continuously recurrent erythema multiforme and ring-shaped centrifugal erythema. In the group of patients, high levels of induced IL-17 production may indicate a presence of an autoimmune component in pathogenesis of the disease and/or reflect the severity of its course. The effectiveness of therapy in the examined patients correlated with ability of cultured blood cells to synthesize and release IL-10. It has been shown that high values of spontaneous and induced IL-10 production are associated with a good response to therapy (significant clinical improvement, long-term clinical remission). Meanwhile, low values of spontaneous and induced IL-10 production were detected in patients with weak therapeutic effect (rapid development of relapses following the course of therapy). The data obtained suggest a probable prognostic significance of these substances as clinical biomarkers. The determination of these cytokines in blood cell cultures in patients with the studied pathologies may improve the assessment of therapeutic efficiency and predict the course of the disease. However, further research is needed in this area, including other types of clinical disorders.

Desminopathies are considered rare or so-called “orphan” diseases. Therefore, little is known about sensitivity of these patients to allergens and physical factors. The aim of our report was to investigate the allergic status of a patient with desminopathy carrying T341P mutation in a heterozygous state. The retrospective study is based on a case of familial desminopathy identified in South-Western Siberia. Quantitative analysis of total and specific immunoglobulins in blood and coprofiltrate of a proband with desminopathy was carried out by means of turbidimetric and chemiluminescence immunoassay, enzyme allergosorbent testing, and ELISA technique. The proband with desminopathy was diagnosed with polyvalent allergy to plant-, food- and infectious allergens. Specific IgE antibodies to pollen of early-blooming meadow grasses and Secale cereale, as well as to cow’s milk, Mucor racemosus and Fusarium moniliforme fungi were found in the blood. Coprofiltrate from the patient revealed specific IgE to pollen of early-blooming meadow grasses and trees, as well as to chicken eggs and casein. Whereas total serum IgE level at the onset of clinical desminopathy symptoms showed two-fold increase over the reference values, it was decreased by 5.5 times over the past 10 years. Over the last two years, the total concentration and average level of specific IgG4 antibodies to food allergens in blood increased by 15%. Provocation tests for cold- and cholinergic urticaria were positive. A respiratory allergy, which emerged by the age of 20 could be the probable trigger of clinical events in desminopathy with T341P mutation. Just by this age, the proband developed ventricular extrasystolia, as well as a barely felt decrease in physical strength. Then, since the age of 30, there was a progressive weakness of the skeletal muscles and a noticeable decrease in physical strength, followed by whole-scale development of the disease, which became severe after 40 years old. Being combined with excessive colonization of intestinal and oral microbiota, and increased endotoxin levels, the polyvalent allergies with high concentration of specific IgG4 antibodies and other (sub)classes may participate in pathogenesis of T341P desminopathy.

Prevalence of metabolic syndrome in the world is 20-40%. Due to the high occurence of metabolic syndrome, its early detection is of great importance for timely initiation in order to prevent its eventual complications. Researchers still do not achieved consensus on etiology, diagnosis and treatment of metabolic syndrome. Currently, it has only been shown that there are risk factors for the development of metabolic syndrome such as genetics, lifestyle and disorder of the normal qualitative and quantitative composition of the microbiota. In our opinion, chronic sluggish inflammation and microbiological intestinal dysbiosis play an important role in development of metabolic disorders, and the key predictor of their development is the state of food hyperreactivity. The aim of our work was to assess the role of food hyperreactivity in development of chronic inflammation, metabolic disorders, intestinal dysbiosis and relationships between microbiota, inflammation indexes and metabolic disorders. To achieve this goal, specific IgG antibodies to 111 food antigens were determined using the immunohealth methodology (RZN 2020/9970). Moreover, biochemical indicators of lipid and carbohydrate metabolism, proinflammatory cytokines (IL-6, IL-17), a complete blood count and 33 indicators of intestinal microbiota using PCR (COLONOFLOR-16 (premium)) were evaluated. The study included 60 patients with increased body mass index and 20 volunteers with a normal body mass index. The study material included venous blood samples and fecal samples. The concentrations of cytokines, insulin, and biochemical indicators were determined in blood serum samples. Fecal specimens were used to assess the qualitative and quantitative composition of the colon microbiota. We obtained data indicating the role of food hyperreactivity in development of chronic inflammation and metabolic disorders. We have also shown the role of individual members of intestinal microbiota and their relationship to inflammation and development of metabolic disorders. Thus, we demonstrated an integral relationship between food hyperreactivity, intestinal microbiological dysbiosis, inflammation indices and markers of metabolic disorders. These data may serve as a basis for new approaches to prevention and correction of metabolic syndrome, as well as for further studies of microbiota in various disorders.

Abnormal uterine bleeding (AUB) is frequently observed during menopausal hormone therapy (MHT), thus significantly impairing the quality of life of postmenopausal women and reducing their adherence to treatment. In most cases, AUB associated with MHT is not linked to pathological changes of endometrium. Of note, the role of uterine natural killer (uNK) cells in this process remains unexplored. Our objective was to evaluate the role of uNK cells in pathogenesis of AUB in women receiving MHT. A randomized controlled trial was conducted at the N. Pirogov City Clinical Hospital No. 1 from November 2022 to October 2024, involving 75 postmenopausal women. The participants were divided into three groups: women receiving MHT with AUB (n = 27); females receiving MHT without AUB (n = 25), and postmenopausal women not receiving MHT (n = 23). To perform immunohistochemical analysis and flow cytometry, endometrial samples obtained via pipelle biopsy were examined in a control group (not receiving MHT), and in the study group before MHT initiation, after 6 months of MHT treatment, and during AUB episodes. Women with AUB during MHT exhibited a statistically significant increase in uNK cells in endometrial samples compared to those without AUB (CD3^-/CD16⁺/CD56⁺: 1.7 (1.46-1.85) vs. 0.66 (0.5-0.79), p < 0.001). Immunohistochemical analysis revealed an increased density of CD56⁺ cells in endometrial stroma of patients with AUB during MHT. These findings confirm a role of uNK cells in pathogenesis of AUB in women receiving MHT. Further research may contribute to the development of new approaches for prevention and treatment of AUB by means of modulating the uNK cell activity.

Macrophages are actively involved in recognition, capturing, and destruction of foreign pathogens, as well as removal of cellular debris. The most important role of macrophages is to initiate and regulate the inflammatory response: they synthesize and secrete a wide range of proinflammatory cytokines that activate other immune cells and promote the development of inflammation. The functional state of macrophages directly depends on mitochondrial activities, both as energy suppliers, and as key participants in signaling pathways associated with production of reactive oxygen species and inflammasome activation. Mitochondrial dysfunction may lead to excessive macrophage activation and chronic inflammation, typical of diseases like atherosclerosis and metabolic disorders. Damaged mitochondria release components such as mtDNA and cardiolipin, potentially triggering autoimmune responses. To prevent these events, the cells are capable of mitophagy, a selective autophagy process that removes dysfunctional mitochondria via the lysosomal pathway. Polyunsaturated fatty acids are known to influence inflammation and mitochondrial function, including mitophagy. Arachidonic acid, a precursor of prostaglandins and leukotrienes, modulates immune responses, but its role in mitophagy remains unclear. The aim of this study was to investigate whether arachidonic acid affects mitophagy and the proinflammatory response of human macrophages. Primary monocytes were isolated from whole blood of healthy donors and differentiated into macrophages over 5 days. The cells were treated with 20 μM arachidonic acid for 24 hours, followed by 1 μg/mL LPS stimulation for another 24 hours. Cytokine secretion (TNF, IL-6, IL-8, CCL2) was measured by ELISA technique. Mitophagy was assessed using confocal microscopy by evaluating co-localization of mitochondrial and lysosomal dyes. The results showed that arachidonic acid enhanced mitophagy and reduced secretion of TNF, IL6, and CCL2 in response to LPS. These findings suggest that activation of mitophagy may contribute to the anti-inflammatory effects of arachidonic acid in macrophages.

Labor activity, terms of exposure to professional factors and work experience contribute to modulation of both physiological and psychological functions of the human body. Ecological and climatic features of high latitudes, characterized by almost year-round low temperatures, reduced UV insolation and altered photoperiodism lead to adverse impact of professional activity. The complex of professional and environmental factors is stressful for adaptive abilities, including immune system. The aim of our study was to assess the influence of work experience on the state of immune homeostasis in hydrographers at the Northern Fleet of Russian Federation. A total of 64 practically healthy men working under the conditions of Northern seas were examined, depending on the length of their service: (1) work experience of 2.3±0.4 years; (2) 9.0±0.5 years; (3) 15.9±0.6 years; (4) 28.9±1.0 years. The number of lymphocytes (CD5⁺, CD10⁺, CD95⁺, CD71⁺) and the ratio of their contents (CD10⁺/CD95⁺ and CD71⁺/CD95⁺) were determined in peripheral blood using the indirect immunoperoxidase reaction technique with monoclonal antibodies on dried-drop lymphocyte preparations with a peroxidase conjugate stained with a chromogenic solution. The data analysis showed that the number of CD5⁺ lymphocytes decreases in individuals with up to 9.0±0.5 years of work experience. The ratios of the cell contents CD10⁺/CD95⁺, and CD71⁺/CD95⁺ varied from 0.94 to 1.06, being within optimal reference values 1±0.05, without any statistically significant difference depending on the length of service. It was found that the suggested mechanisms of immune adaptation proceeds in two ways: in young hydrographers with short and intermediate working experience it is implemented via maintenance of lymphoproliferation-to-apoptosis ratio, due to CD10⁺/CD95⁺, along with decreased levels of CD5 marker expression. In older hydrographers with significant and long-term work experience, it proceeds via restoration of CD5 marker expression, along with expanded distribution range of CD10/CD95 ratio and maintenance of CD71⁺/CD95⁺ ratio within strict limits. The obtained results suggest a need for individual medical and biological monitoring in order to correct the immune homeostasis of the people working in high latitudes.

Acute respiratory viral infection (ARVI) is one of the causes of global morbidity. Arterial hypertension (AH) is the most common chronic non-infectious disorder, which may be accompanied by ARVI occurence. The aim of the study is to investigate the clinical features of ARVI of various etiologies (COVID-19, influenza, and unspecified) in patients with arterial hypertension. The retrospective, comparative study included 535 patients divided into three groups: ARVI of unspecified etiology (group 1), 249 persons; COVID-19 (group 2), 250 patients; influenza (group 3), 36 cases. Each of the three groups included two subgroups: A, only ARVI (unspecified, COVID-19, influenza); B, ARVI (unspecified, COVID-19, influenza) accomplished by AH conditioin. Statistical data processing was carried out using STATISTICA 10.0 software packages. The manifestations of intoxication and catarrhal syndrome occurred in patients of subgroups 1A and 1B, their severity was different. In respondents with ARVI and AH (subgroup 1B), the course of ARVI differs in the following parameters: runny nose (χ² = 4.3; p = 0.040), sore throat (χ² = 4.3; p = 0.037), fever to febrile levels (χ = 24.5; p = 0.000). The clinical picture in patients with COVID-19 + hypertension differed from patients with COVID-19 without hypertension in that more patients had anosmia (χ² = 3.84; p = 0.050), headaches (χ² = 3.84; p = 0.050), myalgia (χ² = 4.38; p = 0.036), sleep disorders (χ² = 4.11; p = 0.043), cough (χ² = 4.18; p = 0.041), prolonged febrile fever (U = 2.01; p = 0.044) (χ² = 5.74; p = 0.017). Patients with influenza and AH were more likely to report nasal congestion (χ² = 9.93; p = 0.002), cough (χ² = 4.11; p = 0.043), and fever (χ² = 11.25; p = 0.000), which lasted up to 8.5 days (U = 2.59; p = 0.023). For all patients, regardless of the genesis of ARVI in the presence of AH, febrile fever was more common and longer. The manifestations of intoxication and catarrhal syndrome in patients with influenza + AH are distinguished by the complaints of nasal congestion, cough and sleep disorders. In normotensive patients with COVID-19, loss of smell, headache, myalgia, sleep disorders were more common. Knowledge of the clinical features of the course of ARVI of various etiologies in patients with AH will allow for timely therapy correction of both ARVI and AH at the early stages.