The state of cytokine regulation and endothelial dysfunction in the combined course of vibration disease and arterial hypertension

Background. The article presents data on the state of cytokine regulation, indicators of endothelial damage when exposed to industrial vibration (general, local) and in combination with arterial hypertension. Aim. To improve the quality of early diagnosis and prevention of vibration disease in an isolated course and its combination with arterial hypertension based on a study of the cytokine profile, biomarkers of endothelial dysfunction in this pathology. Materials and methods. A comprehensive survey of 84 patients with isolated vibration disease from the effects of local, general, first, second degree and 61 patients with a combined course of vibration disease from the effects of local, general second degree vibration and arterial hypertension, 30 people in the control group without contact with industrial vibration and found healthy by medical examination. The levels of pro-inflammatory (IL-1, IL-8, TNF-) and anti-inflammatory cytokines (IL-4), biomarkers of endothelial damage (EDN-1, TGF-1, VEGF-A, PDGF-BB, fibronectin, Willebrand factor) were determined using the enzyme immunoassay method. Results. The response of the immune system to the effects of industrial vibration is characterized by a cytokine imbalance an increase in the level of pro-inflammatory cytokines (IL-1, IL-8, TNF-) and a decrease in the level of anti-inflammatory cytokine (IL-4). With a combined course of vibratory disease and arterial hypertension, the cytokine imbalance is characterized by an even more significant increase in serum IL-1, IL-8, TNF- and a decrease in serum IL-4 concentration. Endothelial dysfunction with WB from the action of both local and general vibration in combination with hypertension is characterized by a significant increase in serum EDN-1, TGF-1, VEGF-A, PDGF-BB, fibronectin, Willebrand factor. Conclusion. The study of the cytokine profile, biomarkers of damage to the vascular endothelium in this pathology will allow for the early diagnosis of vascular disorders and to optimize preventive measures for workers in vibration-hazardous industries.

Comprehensive mapping of the human cytokine gene regulatory network

Proper cytokine gene expression is essential in development, homeostasis and immune responses. Studies on the transcriptional control of cytokine genes have mostly focused on highly researched transcription factors (TFs) and cytokines, resulting in an incomplete portrait of cytokine gene regulation. Here, we used enhanced yeast one-hybrid (eY1H) assays to derive a comprehensive network comprising 1380 interactions between 265 TFs and 108 cytokine gene promoters. Our eY1H-derived network greatly expands the known repertoire of TF–cytokine gene interactions and the set of TFs known to regulate cytokine genes. We found an enrichment of nuclear receptors and confirmed their role in cytokine regulation in primary macrophages. Additionally, we used the eY1H-derived network as a framework to identify pairs of TFs that can be targeted with commercially-available drugs to synergistically modulate cytokine production. Finally, we integrated the eY1H data with single cell RNA-seq and phenotypic datasets to identify novel TF–cytokine regulatory axes in immune diseases and immune cell lineage development. Overall, the eY1H data provides a rich resource to study cytokine regulation in a variety of physiological and disease contexts.

CYTOKINE REGULATION OF THE IMMUNE RESPONSE IN PATIENTS WITH ACUTE NECROTIC PANCREATITIS COMPLICATED BY MULTI-ORGANIC FAILURE

Aim: To study the cytokine regulation of the immune response in patients with acute necrotic pancreatitis (ANP) complicated by multiple organ failure (MON). Material and methods: A prospective cohort study of 22 patients with ANP complicated by MON who were treated in the clinic during 2014-2020 has been performed. We studied changes in blood cells expressing clusters CDIIa +, CD162 +, CD95 +, CD16 +, HLA-DR + molecules, levels of interleukins IL-2, IL-4, IL-6. The efficacy of treatment was determined by the duration of the organ failure, the level of postoperative complications and mortality. Results: Low expression of CD11a + and CD162 + on immunocompetent cells together with two time reduction of the content of CD95 + cells was observed in patients with ANP complicated by MON, which caused a decrease in the concentration of IL-6 at the same time with a slight increase in IL-4. A permanent reduction of the content of CD11a+-, CD162+- and CD95+-leukocytes simultaneously with a drop of the concentration of IL-4 and an excessive increase in the levels of IL-2 and IL-6 was associated with a negative course of the disease. Conclusions: The imbalance of cytokine regulation of the immune response develops in patients with ANP, complicated by MON. Progressive and excessive increase of plasma concentrations of IL-2 and IL-6 occurs as well as complete absence of IL-4 occurs in patients with an adverse course of the disease.

Cytokine regulation of immune status of patients of older age groups with odontogenic phlegmon of maxillofacial region on background of immunocorrective therapy

The influence of the immunomodulator azoximer bromide has been studied on the cytokine regulation of immune status at elderly and senile patients with the odontogenic phlegmon of the maxillofacial region. Clinical and immunological studies of 95 elderly and senile patients with the odontogenic phlegmon of the maxillofacial region were carried out. The authors has been shown including in the scheme of traditional treatment of this disease of azoximer bromide allows to normalize the cytokine regulation of immune status, that enhances the effectiveness of treatment and decreases the term of the patients’ treatment at the hospital.

Comprehensive mapping of the human cytokine gene regulatory network

SummaryProper cytokine gene expression is essential in development, homeostasis, and immune responses. Studies on the transcriptional control of cytokine genes have mostly focused on highly researched transcription factors (TFs) and cytokines, resulting in an incomplete portrait of cytokine gene regulation. Here, we use enhanced yeast one-hybrid (eY1H) assays to derive a comprehensive network comprising 1,380 interactions between 265 TFs and 108 cytokine gene promoters, greatly expanding the known repertoire of TF-cytokine gene interactions. We found an enrichment of nuclear receptors and confirmed their role in cytokine regulation in primary macrophages. Additionally, we used the eY1H-derived network as a framework to identify pairs of TFs that synergistically modulate cytokine gene expression, and to identify novel TF-cytokine regulatory axes in immune diseases and immune cell lineage development. Overall, the eY1H data provides a rich resource to study cytokine regulation in a variety of physiological and disease contexts.

Influence of Helicobacter pylori on cytokine regulation in chronic atrophic gastritis

At present, the level of Helicobacter pylori infection is determined by geographic area, gender and age of the examined individuals, and can reach up to 95% of the total population. Environmental adaptation of H. pylori is exhibited in its ability to adhere to the gastric mucosal epithelium and modulated expression of its own virulent factors. Current concepts implicate that H. pylori can survive inside epithelial cells, evading host immune response. Cytokines are produced by immune cells and act to regulate its major stages. A cytokine cascade launched after Helicobacter pylori infection triggers immune reactions, progression of chronic inflammatory and destructive processes in the gastric mucosa. The role of cytokines in precancerous diseases of the stomach is ambiguous because, on the one hand, they activate immune response aimed at eliminating the pathogen, whereas on the other hand, they do contribute to the disease progression. The aim of our study was to examine profile of some cytokines and features of cytokine regulation in H. pylori-infected middle-aged males with chronic gastritis (CG) as well as chronic atrophic gastritis (CAG). In patients with CG with H. pylori, CAG and CAG with H. pylori, an increase in the cytokine IL-2 was observed that might contribute to augmented damaging effect of cytotoxic lymphocytes, as well as implementation of antitumor effect. CAG with H. pylori was featured with IL-8 hyperproduction, which resulted in increased absolute numbers of band neutrophils in peripheral blood and their decreased phagocytic activity evidencing about altered host defense mechanisms. There was increased amount of IFNy involved in recognition of malignantly transformed cells and upregulated expression of the major histocompatibility complex molecules on antigen-presenting cells. In patients with CG with H. pylori and CAG with H. pylori, production of IL-4 was increased, which might serve as a contributing factor to the chronicity of H. pylori-associated diseases. Overproduction of type 1 and type 2 cytokines indicates about activated Th1 and Th2 type immune reactions in H. pylori-associat-ed CG. A potent pro-inflammatory cytokine cascade triggers inflammatory changes in gastric mucosa with developing neutrophil infiltration and lymphocyte activation. Damage and death of epithelial cells upon inflammation form erosive and ulcerative defects, or changes manifested as gastric mucosal atrophy, metaplasia and neoplasia. The data obtained may be used as additional diagnostic criteria in early diagnostics of precancerous stomach diseases.