Pathogenetic role of cytokines in hemorrhagic fever with renal syndrome in dynamics and disease of various severity

The aim of the work is to determine the relationship between the levels of cytokines of proinflammatory and anti-inflammatory action during the clinical course of hemorrhagic fever with renal syndrome (HFRS) and the previously described characteristics of the phenotypic composition of blood lymphocytes in disease of various severity. Materials and methods. 65 patients with a serologically verified diagnosis of HFRS were under observation. The control group included 15 conditionally healthy people. Determination of cytokines in the blood of patients with HFRS was carried out by the enzyme immunoassay method at the different stages of the disease. The phenotypic composition of blood lymphocytes was assessed by flow cytofluorimetry. Results. At the different stages of the disease, there was a quantitatively different increase in the content of cytokines in the blood associated with cytotoxic immune reactions (IL-12, IFN, TNFa, TNF), as well as IL-10 and IL-6 correlated with each other in severe cases, against the background of a drop in blood levels of IL-4 and IL-1. In the moderate course of HFRS, correlations of IL-12 and IL-4 with NKG2D+ CTL, the relationship of IL-12 with almost all other cytokines, and the correlation of CD8+ Treg with IL-6 and TNF levels were observed. In severe cases, the formation of a complex that included interconnected IL-6 and IL-10 correlating with the number of NKG2D+ CTL, CD8+ Treg, NKT was noted. Conclusion. The pathogenetically significant mechanism of HFRS is realized with the predominant participation of cytokines of the cellular immune response and IL-6, correlatively associated with NKG2D+ CTL, CD8+ Treg, NKT, which, in case of a favorable outcome, contribute to the active formation of a pool of CD8+ memory cells, disrupted presumably by excessive secretion of IL-10

Bacteria of genus <i>Filifactor</i> in patients with periodontitis and type 2 diabetes in accordance with metagenomic analysis of the periodontal microbiome

Introduction. Periodontal diseases are a common pathology with chronic periodontitis (CP) being the most severe form. This polymicrobial disease has become a problem of great importance in recent years due to the possibility of development of systemic effects associated with this condition. CP is often combined with type 2 diabetes (T2D). The main cause of the occurrence and development of periodontal pathology is played by the bacteria Filifactor alocis, the least studied and most recently discovered periodontal pathogen. The objective of this study was to identify bacteria of genus Filifactor as part of the periodontal microbiome associated with CP and T2D and to clarify the mechanisms of their possible influence on associated metabolic processes according to comparative metagenomic analysis. Materials and methods. A metagenomic study of the microbiome of periodontal pocket samples from 28 patients with CP associated with T2D and 22 patients with CP, as well as the microbiome of dental gingival sulcus samples from 19 clinically healthy individuals was performed. 16S-sequencing of the ribosomal RNA gene was used to determine the taxonomic composition of the microbiome. Prediction of metabolic pathways involving the microbiome was performed with the help of the shotgun method. Results. Filifactor bacteria were the one of the most frequent microorganisms only in patients with CP associated with T2D. The rate of identification of these bacteria was correlated with low predicted metagenomic levels of fatty acid biosynthesis and pyrimidine metabolism in the affected area. Conclusion. The detection frequency of Filifactor bacteria in patients associated with CP and T2D is negatively correlated with the selected features of putative metabolic pathways of the microbiome, which include fatty acid biosynthesis and pyrimidine metabolism

Cytokine Profile as a Marker of Cell Damage and Immune Dysfunction after Spinal Cord Injury

The study reviews findings of the recent experiments designed to investigate cytokine profile after a spinal cord injury. The role of key cytokines was assessed in the formation of cellular response to trauma. The specific immunopathogenic interaction of the nervous and immune systems in the immediate and chronic post-traumatic periods is summarized. The practicality of a step-by-step approach to assessing the cytokine profile in spinal cord injury is shown, the need to take into account the combination of pathogenetic and protective components in the implementation regulatory effects of individual cytokines, their integration into regenerative processes in the damaged spinal cord, which allows a rational approach to the organization of the treatment process and the development of new medicines

Diagnostic significance of TLR2 and TLR4 receptors on lymphoid cells as a marker of the progression of periodontal inflammation associated with key periodontal pathogenic species <i>F. alocis</i> and <i>P. gingivalis</i>

The aim of the work was to evaluate the diagnostic value of TLR2 and TLR4 expression on periodontal and peripheral blood lymphoid cells by immunofluorescence microscopy in patients with chronic periodontitis associated with key periodontal pathogenic species Filifactor alocis, Porphyromonas gingivalis. Materials and methods. The study included 150 patients 88 (59%) women and 62 (41%) men aged 18 to 73 years with chronic periodontitis in the acute phase (CP) and 32 people without signs of chronic periodontal inflammation. To confirm the diagnosis of periodontitis, the Multident-5 PCR kit was used (detection of P. gingivalis, Prevotella intermedia, Tannerella forsythia, Treponema denticola, Aggregatibacter actinomycetemcomitans), as well as rt-PCR for F. alocis and P. gingivalis in the contents of the periodontal pocket (NPF GenLab, Russia). To evaluate cells carrying CD282 and CD284 markers, gingival fluid flushes from the periodontal pocket with Hanks' solution were used. The isolated cells were stained with antibodies to CD282 markers (corresponding to TLR2 receptor) or CD284 (corresponding to TLR4 receptor) labeled with FITC, and fixed with paraformaldehyde for subsequent immunofluorescence microscopy. Results. The expression of TLR2 and TLR4 on peripheral blood and gingival fluid leukocytes was studied in individuals with healthy periodontitis and patients with chronic periodontitis associated with F. alocis, P. gingivalis. According to the results of PCR, the detection rate of F. alocis and P. gingivalis was 64 and 62.7%, respectively, which confirmed their dominance in the microbial association. It was found that the expression of TLR2 and TLR4 on peripheral blood lymphoid cells varied in humans. The possible diagnostic significance of this phenomenon in assessing the progression of chronic periodontitis is discussed. Conclusion. In patients with chronic periodontitis associated with the dominance of periodontopathogenic species F. alocis, P. gingivalis, the multidirectional expression of TLR2 and TLR4 on peripheral blood cells was observed, which may have diagnostic significance in assessing the progression of periodontal diseases

Plasma Cytokines Level and Spinal Cord MRI Predict Clinical Outcome in a Rat Glial Scar Cryoinjury Model

Traumatic injury of the spinal cord is still one of the most challenging problems in the neurosurgical practice. Despite a long history of implementation of translational medicine in the field of spinal cord injury (SCI), it remains one of the most frequent causes of human disability and a critical situation for world healthcare systems. Here, we used our rat model of the of unilateral controlled SCI induced by a cryoinjury, which consistently reproduces glial scarring and posttraumatic cyst formation, and specifically evaluated histological, bioimaging and cytokine data. We propose a 10-grade scoring scale, which can objectively estimate the extent of damage of the experimental SCI according to the magnetic resonance imaging (MRI) results. It provides a homogeneous and reliable visual control of the dynamics of the posttraumatic processes, which makes it possible to clearly distinguish the extent of early damage, the formation of glial scars and the development of posttraumatic syringomyelic cysts. The concentration of cytokines and chemokines in the plasma following the experimental SCI increased up to two orders of magnitude in comparison with intact animals, suggesting that a traumatic injury of the spinal cord was accompanied by a remarkable cytokine storm. Our data suggested that the levels of IL-1&alpha;, IL-1&beta;, TNF&alpha;, GRO/KC, G-CSF, IFN&gamma; and IL-13 may be considered as a reliable prognostic index for SCI. Finally, we demonstrated that MRI together with plasma cytokines level directly correlated and reliably predicted the clinical outcome following SCI. The present study brings novel noninvasive and intravital methods for the evaluation of the therapeutic efficacy of SCI treatment protocols, which may be easily translated into the clinical practice