Vol 21, No 1 (2018)

Infection is one of the leading causes of mortality and morbidity in the world. Neutrophils are an active and numerous effector link in the innate immune system, which protects the body from infection with pathogenic microorganisms. However, the contribution of neutrophils in the development of the infectious process was underestimated, despite the fact that the functions of this subclass of leukocytes have long been known as a pathogenetic element of inflammation. In addition to phagocytosis, these cells can mediate lesser-characterized antibacterial strategies – extracellular degranulation, and also, by releasing extracellular chromatin, nuclear protein and serine proteases, to form web-like fiber structures called neutrophilic extracellular traps (NETs). NETs can capture pathogens, cause endothelial dysfunction and pro-inflammatory immune responses. The phenomenon of NETs is a relatively new form of programmed cell death (NETosis), the significance of which in the development of the infectious process and the development of inflammation is not fully understood. NETosis has a high potential for further study of the pathogenesis of inflammation and the search for effective methods of treating infections. This review focuses on modern data on the basic protective strategies of neutrophils against bacterial infections and their contribution to the pathogenesis of proinflammatory reactions. Modern approaches to pharmacological modulation of various variants of antimicrobial mechanisms of neutrophils are discussed, which is promising in cases of complex treatment of infections associated with antibiotic-resistant strains of bacteria.

Interleukin‑17 (IL‑17) is one of the inflammatory cytokines, which enhances including the effects of other pro‑inflammatory cytokines. In order to increase the statistical power and increase the reliability of the results according to various researchers, including as a result of its own research, conducted a meta‑analysis (a quantitative systematic review) study of IL‑17 in peripheral blood of patients with influenza A (H1N1) pdm09. Question: to determine with a high level of confidence, whether IL‑17, a marker of prognosis of influenza A (H1N1) pdm09. Searches were carried out research work on this subject in a variety of electronic databases (Medline, EMBASE, the Cochrane Controlled Trials Register, and others.), in dissertations, journals, thematic reviews, conference proceedings and other sources. 3 scientific papers were selected that met the criteria for inclusion / non‑inclusion in the study (characteristic of scientific papers, diagnostic criteria, age of patients, comparable groups of patients, the presence of self‑control, comparable research methodology, statistical criterion and the total number of independent studies). Selected studies have shown sufficient uniformity (homogeneity) comparison groups. This meta‑analysis of scientific papers showed that the determination of serum IL‑17, patients with severe influenza A (H1N1) pdm09 allows a high probability of predicting a favorable outcome. At the same time, the frequent unfavorable outcome of the disease (with a probability of 90% or more) indicates the absence in the serum of patients with influenza A (H1N1) pdm09 IL‑17 (below the threshold of sensitivity of diagnostic test kits). Thus, the results of a meta‑analysis of IL‑17 level in the blood can be used in clinical medical practice for quite simple and convenient prognosis marker of influenza A (H1N1) pdm09.

To establish a definitive molecular diagnosis for the case of a 17-Year-Old Boy (NS) with a history of CVID, recurrent pulmonary infections, chronic EBV viremia, lymphadenopathy and a decrease of IgG3 and luck of IgG4 who presented for follow-up in the immunodeficiency clinic whole exome capture and next-generation sequencing were performed. We showed a presence of heterozygous missense mutation E1021K in the PIK3CD gene that encodes p110d (c.3061G > A [p.E1021K]). The mutation was verified by Sanger sequencing and not found in parents genomic DNA, thus classifying this E1021K mutation as de novo. Several additional mutations relevant to immune system pathways were found and confirmed by Sanger sequencing including TLR3 p.L412F, TNFRSF1A p.R121Q (rs4149584), associated with periodic disease.

The results of research on two models of acute bronchitis induced by cigarette smoke and formaldehyde, in rats the substance of glycosylated polypeptides complex (GPC) provided anti-inflammatory effect. Based on these data, a search of anti-inflammatory action mechanisms of GPC. The aim of the study was to investigate the activity of GPC obtained from viscera of sea urchins S. droebachiensis on two cyclooxygenase isoforms (COX1 and COX2), 5 – lipoxygenase (5-LOX), lipopolysaccharide (LPS)-induced p38 mitogen-activated protein kinase (MAPK) phosphorylation, toll-like receptor 4 (TLR4). COX1/2 and 5-LOX activity studied using commercial kits (Cayman Chemicals, USA). GPC effects on LPS-induced p38 MAРK phosphorylation were studied using human monocyte cellline U937. To assess the interaction of GPC with toll-like receptor 4 (TLR4) cell line HEK-Blue-hTLR4 (Invivogen, USA) was used. Results of the study showed that GPC inhibited COX2 activity with IС50 67 µg/ml. Also, GPC inhibited LPS-induced p38 MAРK phosphorylation by blockade of TLR4 with ЕС50 2.7 µg/ml. In the other hand, GPC did not affect the activity of COX1 and 5-LOX. The obtained results allow to conclude that targets of GPC anti-inflammatory action are: COX2, of p38 MAРK and TLR4.