Search

Adult-onset Still’s disease (AOSD) is a rare complex autoinflammatory disease of unknown etiology. The main problem, practitioners have been facing with when researching AOSD, is the lack of developed approaches to assessing the activity of the disease. Traditionally used standard markers of inflammation do not always reflect the real activity of AOSD, especially when a patient is already receiving anti-inflammatory therapy. The article presents original data on the study of biomarkers: interleukin-1 beta (IL-1b), interleukin-6 (IL-6), interleukin-18 (IL-18), ferritin, glycosylated ferritin, calprotectin, procalcitonin compared with C-reactive protein, leukocyte and neutrophil counts in patients with moderate and high activity of AOSD. The relationship between inflammatory biomarkers and the Pouchot systemic score was evaluated to identify promising laboratory indicators of disease activity.

Background. Currently, diabetes mellitus is the most common of all endocrine diseases with increasing tendency. The purpose of our research was to study the dynamics of serum levels of proinflammatory cytokine-IL-1β in streptozotocin-induced diabetes. Materials and methods. The experiments were performed on 88 white male Wistar rats weighing 170-210 g. Animals were divided into three groups: 1 - intact; 2 - control; 3 - experimental with a model of diabetes mellitus, which was reproduced by intraperitoneal injection of streptozotocin by “Sigma" company (USA), diluted in 0.1 M citrate buffer with a pH of 4.5, at a rate of 60 mg/kg body weight. The control group of animals received an intraperitoneal injection with an equivalent dose of 0.1 M citrate buffer solution with a pH of 4.5. All studies were performed under thiopental-sodium anesthesia at a rate of 60 mg/kg body weight. Serum levels of IL-1β were determined by enzyme-linked immunosorbent assay (ELISA) kit (Elabscience, USA) according to the manufacturer's instructions 14, 28, 42 and 70 days after streptozotocin injection. The STATISTICA 10 program was used for statistical processing of the obtained results. Results. Conducted biochemical analysis showed that in animals with streptozotocin-induced diabetes there was an increase in the content of proinflammatory cytokine IL-1β compared with similar indicators in the control group of animals at all stages of the experiment: after 14 days by 22.5%, after 28 days by 40.2%, after 42 days by 72.8% and after 70 days by 107.2%. Conclusion. The obtained results suggest that pro-inflammatory cytokine interleukin-1β plays one of the leading roles in the pathogenesis of streptozotocin-induced diabetes, as indicated by a significant increase in serum of this cytokine at all stages of the experiment.

243 primary teeth in 112 children aged 3-8 years were treated using pulpotomy. The medicines «Pulpotek», «Trioxident» and «Viskosta» in combination with Zinkoxid Eugenol were used to cover the pulp stump. The reaction of immunocompetent cells of the teeth pulp to the above-mentioned medicines was studied in 48 teeth. 12 months later, after the treatment of pulpitis with Pulpotek and Viskostat combined with Zinkoxid Eugenol, the level IL 1β and TNF-α in the samples of the pulp tissue had no significant difference comparing with the normal index. There was no normalization of the pulp tissues in 33,3% of cases of pulpitis treatment with Trioxident that proved a decrease of the IL 1β level and an increase of that of TNF-α in the samples of the pulp tissues extracted after using this method

Idiopathic recurrent pericarditis (IRP) and adult-onset Still's disease (AOSD) are polygenic autoinflammatory diseases, in the pathogenesis of which pro-inflammatory cytokines from the interleukin-1 superfamily play a central role.Aim. To compare serum concentrations of proinflammatory cytokines and glycosylated ferritin (GF) in patients with IRP and AOSD during an exacerbation.Material and methods. The study included 15 patients with AOSD, 15 — IRP. The diagnosis of AOSD was established using the Yamaguchi criteria (1992). IRP was diagnosed in accordance with the 2015 European Society of Cardiology on the diagnosis and management of pericardial diseases. Blood sampling from all patients was carried out during the recurrence period prior to the anti-inflammatory therapy initiation. The serum levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-18 (IL-18), procalcitonin, total ferritin and GF was assessed. The results obtained were compared with levels of biochemical parameters, high-sensitivity C-reactive protein (CRP), as well as with white blood cell (WBC) and neutrophil counts.Results. The median age in the AOSD group was 28 years, and the IRP — 55 years. An increase WBC count >10*109/L was detected in 10 and 9 patients in the AOSD and IRP groups, respectively. The concentration of CRP was increased in all patients and did not differ in the study groups (p=0,836).The highest values of ferritin and GF levels were found in the AOSD group (1416 ng/ml vs 408 ng/ml, p=0,008) and (12% vs 33,9%, p=0,067), respectively. In both groups, increased concentrations of IL-6 and IL-18 were determined. In the AOSD group, the concentration of IL-18 was higher than in the IRP group (2114 pg/ml vs 161,5 pg/ml, p

Purpose.To study the immunopathogenetic mechanisms of the functioning of congenital immunity in children with dental and disabling somatic pathology. Materials and methods. A general dental examination was conducted by 416 children with disabilities, who had a dental pathology, aged 2 to 18 years. Yes, I group of observation were 98 children with CNS diseases, II group – 150 children with blood diseases; III group - 70 children with respiratory diseases; IV – 98 children with mental disorders, and the control group V was 50 children without somatic invalidating pathology. The examined children, according to DentalHealthFoundation recommendations, took into account age periods of development of teeth, which correlated with the main stages of childhood and the critical periods of the formation of the immune system: the age of temporary bite (from 2 to 5 years), bite (from 6 to 10 years), constant bite (from 11 to 18 years old). The surveyed methods of research were used: clinical and laboratory – for studying the state of solid teeth tissues, periodontal tissues, oral hygiene; photocolormetric - to study the level of lysozyme, linked immunosorbent assay – secretory immunoglobulin A (sIg A). Microbiological study of plaque and molecular genetics – to determine the expression of the Toll-like receptor (TLR) type 2 and type 4, the nuclear factor kV (NF-κB) and proinflammatory interleukins (IL-1β and IL- 17A) were carried out in 93 children with special needs and caries and chronic catarrhal gingivitis and 25 somatically healthy children. The CFX96 ™ Real-Time PCR Detection Systems (Bio-Rad, USA) amplifier was used to determine the expression level. Specific pairs of primers for analysis of the studied and reference genes were selected using the software Primer-BLAST (NIH, USA) and manufactured by Metabion (Germany). Statistical processing was carried out using the package of the licensed program Statistica for Windows 13 (StatSoft Inc., № JPZ804I382130ARCN10-J). For all types of analysis, the level of statistical significance was used P < 0.05, at which differences were considered reliable. Results. It has been established that in children with disabilities the frequency of caries was registered in the range of 41.67–82.14 %, but in all examined patients in the dental plaque microorganisms such as: Streptococcus non-haemolyticus, Streptococcusheemolyticus, Corynebacterium matruschotti were isolated. In this case, the level of secretory Ig A in the oral liquid in all children with disabilities was in the I group of 0.47 (0.46; 0.48) g / l; in ІІ – 0,45 (0,31; 0,47) g / l; in III – 0,42 (0,41; 0,43) g / l; in IV – 0,33 (0,31; 0,35) g / l, and significantly exceeded the similar indicators in the comparison group – 0,28 (0,26; 0,28) g / l. Lysozyme, by contrast, had a lower level in children with disabling diseases (in the I group it was 5.75 (5.25; 5.89) mg / l; in II – 5.1 (3.25; 5.45) mg/l in the third – 5.74 (5.65; 5.78) mg/l, in IV – 5.62 (5.35; 5.85) mg/l than in the comparison group – 7.26 ( 7,12; 7,45) mg/l. The molecular genetic study of congenital immunity reliably demonstrated a 5.6- and 1.6-fold increase in the transcriptional activity of the mRNA of the TLR2 and TLR4 gene in the buccal epithelium of children with diseases of the central nervous system, 8, 5- and 2.4-fold increase in children with respiratory diseases, 7.8- and 16.6-fold In children with mental disorders, there was no significant change in the level of the mRNA of the TLR2 and TLR4 genes, activation of the pattern recognition receptors causes transcriptional induction of the NF-κB gene and proinflammatory cytokines IL-1β and IL-17A with the epithelium of the buccal epithelium: levels of expression of IL-1β and IL-17A mRNA in children with CNS diseases increased by 8.9 and 7.7 times (P < 0.05), respectively, in children with mental illness, IL-17A levels increased by 2, 2 times (P < 0.05), in children with respiratory diseases and diseases of the system trench expression of IL-1β increased 6.5 and 2.9 times (P < 0.05), respectively, IL-17A - 3.8 and 3.0 times (P < 0.05). Conclusion. The pathogenetic signaling pathways for the implementation of the functioning of congenital immunity depending on the disabling disease and the mechanisms of the formation of odontogenic pathology under the conditions of life of non-hemolytic and hemolytic streptococci and corynebacterium in dental plaque and peculiarities of sIgA products, lysozyme: in children with CNS diseases – due to transcriptional activity of membrane tolu- like receptors 4, expression of the nucleic factor kV (NF-κB) and the activity of the matrix RNA of proinflammatory cytokines IL-1β and IL-17A; with blood diseases - when activating matrix RNA of membrane toluic receptors 2, 4, nuclei factor kV (NF-κB), interleukin 17A; with diseases of the respiratory system - expression of interleukin 17A; with mental disorders - when activating interleukin 1β and membrane toll-like receptors by interleukin 17A.

The article provides a current overview of the correlation between a rare dermatosis — subcorneal pustulosis (Sneddon — Wilkinson disease) — and various diseases of internal organs; features of immunological changes; the role of desmocollin 1, chemoatractants, interleukin-1β, interleukin-6, interleukin-8, interleukin-10, leukotriene B4, tumour necrosis factor-alpha and K5a complement fraction in the pathogenesis of the disease. In this work, the authors describe the features of the clinical picture of the disease, as well as diagnostic criteria, including the use of serum protein electrophoresis. Histological features of the disease are discussed in detail. In addition, modern methods for treating this disease, including the use of dapsone, acitretin, infliximab, PUVA therapy are presented.

BACKGROUND: The study of low-grade inflammation in patients with type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular diseases is a pressing problem. A deeper understanding of the cascade of inflammatory reactions, possibly mediating the severe atherosclerotic lesions of various vascular pools in patients with diabetes, has the potential to introduce more sophisticated diagnostic and therapeutic approaches into practice. AIM: To study the interrelation of low-grade inflammation and atherosclerosis of peripheral arteries in patients with coronary artery disease (CAD) and T2DM. MATERIALS AND METHODS: The study included 137 patients (77 men and 60 women) with CAD. The average age of patients was 62.0 (57.0–66.0) years. The first group included 67 patients with CAD and T2DM, and the second group included 70 patients with CAD. Low-grade inflammation was assessed by the levels of high-sensitivity C-reactive protein, interleukin (IL)-1β, IL-6, IL-8, IL-10 and TNF-α. All patients underwent duplex scanning of carotid arteries and lower extremity arteries (LEAs). RESULTS: Patients with CAD and T2DM showed significantly greater values of stenosis of carotid arteries and LEAs. Direct correlation was revealed between markers of inflammation and the degree of stenosis of the femoral and tibial arteries, as well as the intima-media thickness of the carotid and femoral arteries. In the group of patients with T2DM, the value of IL-1β was 2.04 (0.98–2.52) pg/mL, which was significantly less than 2.43 (1.84–3.19) pg/mL for patients in the second group (p = 0.010). The values of IL-6 were also significantly lower in the first group of patients, at 1.84 (0.73–4.41) pg/mL vs. 3.73 (2.27–10.2) pg/mL in the first and second groups, respectively (p = 0.008). The dose of metformin was inversely correlated with the level of IL-6 (r = −0.314, p = 0.003). CONCLUSIONS: Patients with CAD and T2DM compared with patients without diabetes had significantly greater values of stenosis of peripheral arteries. The levels of IL-1β and IL-6 in the group of patients with CAD and T2DM were significantly lower in comparison with patients without diabetes. The dose of metformin was inversely correlated with the level of IL-6.

According to modern ideas, chronic low-grade inflammation, which development is associated with uncontrolled activation of both innate and adaptive immunity, plays a fundamental role in all stages of the atherosclerotic process. The contribution of inflammation to the development of atherosclerotic vascular lesions attracts attention to the similarity of the mechanisms of immunopathogenesis of atherosclerosis and classic inflammatory rheumatic disease - rheumatoid arthritis. In the aspect of participation in the pathogenesis of atherosclerotic vascular lesions and as a promising therapeutic "target" of particular interest is interleukin-1β (IL-1β), which plays an important role in the development of many acute and chronic immunosuppressive diseases. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "Pro-atherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. The mechanisms of atherosclerosis associated with IL-1β determine the ability of cholesterol crystals and other "proatherogenic" factors to induce the synthesis of IL-1β by activating NLRP3 inflammasome. Convincing evidence for the role of inflammation in development of atherosclerosis in General and good prospects of anti-inflammatory therapy in particular obtained in a randomized placebo-controlled study called CANTOS (Canakinumab Anti-inflammatory Thrombosis Otcomes Study), which studied the effectiveness of treatment with monoclonal antibodies to IL-1β canakinumab (Novartis International AG) in patients with severe atherosclerotic vascular lesions as a new approach to secondary prevention of cardiovascular complications. The results of CАNTOS research, as well as the experience gained in rheumatology in regard to cardiovascular effects of innovative anti-inflammatory drugs, have great importance for the improvement of secondary prevention of atherosclerosis-related cardiovascular complications.

The Aim of the Study: Was to evaluate the effect of selective serotonin reuptake inhibitor fluoxetine on the production of cytokines interleukin-6 (IL-6) and interleukin-1β (IL-1β) by dendritic cells in multiple sclerosis (MS)., Material and Methods: 5 patients with relapsing-remitting MS and five healthy subjects were examined. Levels of IL-6 and IL-1β were measured by ELISA in culture supernatants obtained from lipopolysaccharide stimulated dendritic cells. To assess the effect of fluoxetine on cytokine production, dendritic cells were stimulated in the presence of fluoxetine and antagonists of 5-HT 1A -, 5-HT 2A -, 5-HT 2B -receptors or agonist of 5-HT 2B -receptors., Results: Cytokine production by dendritic cells was comparable in both groups. Fluoxetine suppressed IL-6 and IL-1β production in both groups. Blockade of 5-HT 2B -receptors with specific antagonist RS 127445 reduced the inhibitory effect of fluoxetine on IL-1β production in both groups and IL-6 production in healthy subjects. In contrast, activation of 5-HT 2B -receptors by specific agonist BW 723C86 increased the inhibitory effect of fluoxetine on IL-6 production by dendritic cells in both groups, but did not affect on IL-1β production., Conclusion: These data suggest an anti-inflammatory effect of fluoxetine in MS by modulating pro-inflammatory cytokines production by dendritic cells. This effect could be mediate by activation of 5-HT 2B -receptors.

Interleukin-1β (IL-1β) is the prototypic pro-inflammatory cytokine, whose functions are mediated through interaction with its receptors (IL-1R1 and IL-1R2). Herein, we cloned the full-length cDNA and genomic DNA of IL-1β and IL-1R2 in the Asian swamp eel (Monopterus albus). The eel IL-1β cDNA encodes a putative polypeptide of 246 amino acids. The protein sequence includes a typical IL-1 family signature, but lacked an interleukin-converting enzyme cleavage site. The genomic DNA of eel IL-1β was 2520 bp and comprised five exons and four introns. The eel IL-1R2 cDNA encoded a putative propeptide of 423 amino acid residues, comprising a signal peptide, a transmembrane region and two Ig-like domains in the extracellular region. Similar to other vertebrates, the genomic DNA of the eel IL-1R2 has nine exons and eight introns. Real-time PCR analysis indicated that IL-1β and IL-1R2 were constitutively expressed in all tissues, especially in the liver and immune-related organs. After infection with Aeromonas hydrophila, the transcript levels of IL-1β and IL-1R2 were induced in the head kidney and spleen, reaching their highest levels at 6 h post injection. In vitro, IL-1β and IL-1R2 mRNA levels were also upregulated rapidly at 1h post infection with A. hydrophila. Furthermore, acanthocephalan Pallisentis (Neosentis) celatus could induce the expression of both genes in the head kidney and intestine. In infected intestines, the transcript levels of IL-1β and IL-1R2 were increased by 21.4-fold and 20.8-fold, respectively, relative to the control. The present study indicated that IL-1β and IL-1R2 play an important role in inflammation and host defense, especially in the antiacanthocephalan response.