Acetaminophen is one of the most toxic drugs that can cause liver damage. At the same time, acetaminophen-induced liver failure is closely associated with the development of systemic inflammatory response syndrome. However, there is no drug aimed at suppressing the systemic inflammatory response. That is, this issue needs to be studied experimentally, but a model of systemic inflammation during acetaminophen overdose has not yet been obtained. Therefore, it was decided to develop an experimental model of systemic inflammation during acetaminophen overdose. The purpose of this study was to experimentally substantiate the semi-lethal dose for acetaminophen overdose in C57Bl/6 mice and to evaluate the readings of blood tests after administration of the drug. To determine the semi-lethal dose, male C57Bl/6 mice were intraperitoneally injected with “Ifimol” (Unique Pharmaceutical Laboratories, India) or acetaminophen solution (Sigma-Aldrich, USA) with a concentration of 14 mg/ml in different doses. When introducing “Ifimol”, it was not possible to achieve a semi-lethal dose. When administering a solution of acetaminophen, 50% mortality was recorded at a dose of 600 mg/kg body weight. After establishing a semi-lethal dose, the experimental group was administered an acetaminophen solution (Sigma-Aldrich, USA) with a concentration of 14 mg/ml at a dose of 600 mg/kg. The control group was injected with saline in an equivalent volume. On the second day, liver and peripheral blood samples were taken. Subsequently, hematological and biochemical blood tests and histological analysis were performed. Histological examination revealed centrilobular necrosis and disorganization of the liver structure. According to the biochemical blood test, the activity of aspartate aminotransferase, alanine aminotransferase, creatinine concentration, and the de Ritis coefficient differed statistically significantly (p 0.05) in the experimental group compared to the control group. Among the hematological blood test parameters, there were statistically significant differences in the number of leukocytes, platelets, as well as the absolute and relative content of granulocytes and lymphocytes. Thus, 48 hours after administration of a semi-lethal dose of acetaminophen, there were signs of damage to internal organs (liver, kidneys) and changes in immune system parameters, which are similar to components of systemic inflammation in humans.

Neuroinflammation during intracerebral hemorrhage is initiated by blood breakdown products in the subarachnoid space and/or brain parenchyma. In this case, neuroinflammation can cause the development of systemic inflammation. In some cases, intracerebral hemorrhage is accompanied by the appearance of the phenomenon of ineffective cerebral blood flow and clinical manifestations of brain death. The purpose of the study is to identify markers of systemic inflammation in severe hemorrhagic stroke with or without effective cerebral blood flow. The study included patients with intracerebral hemorrhage and the presence of multiple organ failure syndrome, as well as coma on the first day of manifestation, to determine markers of systemic inflammation. A total of 3 groups were analyzed: patients with ineffective cerebral blood flow (Group 2); with effective cerebral blood flow (Group 3); and control group (Group 1) – healthy blood donors. Criteria for non-inclusion in the study: the presence in patients with hemorrhagic stroke of septic complications during hospitalization and acute infectious diseases during the manifestation of intracerebral hemorrhage. In frozen blood plasma samples (anticoagulant – citrate), the levels of IL-6, IL-8, IL-10, TNFá, procalcitonin, neuron-specific enolase, cortisol, myoglobin, troponin I and D-dimers were determined. Enzyme immunoassay was carried out on an automatic analyzer “Dynex Lazurite” (Dynex Technologies, VA, USA). The Kolmogorov–Smirnov test was used to confirm the normality of data distribution. Further comparison of quantitative data was carried out using the nonparametric Mann–Whitney U test. All results were considered statistically significant at p 0.05. In patients with effective and ineffective cerebral blood flow, statistically significant differences were observed in almost all studied markers of systemic inflammation, except for troponin I. However, in the presence of effective cerebral blood flow, significantly higher values of a number of indicators were noted, which may indicate a more rapidly occurring acute systemic inflammatory response in case of effective cerebral blood flow. At the same time, 28 day mortality and SOFA scores in the group with effective blood flow were lower than in the group with ineffective blood flow. This discrepancy may indicate a greater contribution to 28 day mortality and patient severity from direct loss of brain function than from systemic inflammation in patients with ineffective blood flow. On the other hand, the lack of severity of systemic inflammation in this category of patients is most likely due to impaired blood outflow from the damaged brain and the entry of tissue breakdown products and other pro-inflammatory factors into the systemic circulation. That is, intracerebral hemorrhage is accompanied by the development of neuroinflammation, which may be an important component of systemic inflammation. However, disruption of the inflow and outflow of blood in the main great vessels of the brain reduces the likelihood and severity of the development of systemic inflammation.

Increasing evidence suggests that stroke is a systemic disease affecting multiple organs. Systemic inflammatory response and immune dysregulation associated with hemorrhagic stroke, may play an important role in brain injury, its recovery, and stroke outcomes. However, it is worth of note that, from our point of view, the classical concepts about inflammation in pathophysiology and general pathology do not entirely meet the needs of modern medical practice. The existence of this problem is also typical for assessing pathogenesis, as well as for optimizing pathogenetic therapy of severe strokes. Therefore, within the framework of this work, a dynamic observation and assessment of pathogenesis in severe intracerebral hemorrhage was carried out using the criteria of a systemic inflammation scale. The study included patients with intracerebral hemorrhage and effective cerebral blood flow. Blood sampling was carried out on days 1-3 and 5-7 after clinical manifestation of intracerebral hemorrhage. To determine markers of systemic inflammation in the blood plasma of patients, the levels of IL-6, IL-8, IL-10, TNFá, procalcitonin, cortisol, myoglobin, troponin I and D-dimers were examined using an enzyme-linked immunosorbent assay. The Kolmogorov–Smirnov test was used to confirm the normal data distribution. Further comparison of quantitative data was carried out using the nonparametric Wilcoxon test for paired comparisons. All results were considered statistically significant at p 0.05. In patients on days 1-3 and 5-7, statistically significant differences were not observed in almost all studied markers of systemic inflammation, except for IL-8 and tumor necrosis factor-á. Such increased contents of pro-inflammatory cytokines may indicate increased systemic inflammation over time in the patients with intracerebral hemorrhage and effective cerebral blood flow. Hence, the condition of such patients may worsen on days 5-7 after manifestations of intracerebral hemorrhage, thus requiring more careful monitoring of patients’ blood counts and therapy aimed at suppression of increasing inflammation.

Traumatic brain injury is one of the main causes of both acute and long-term morbidity that concern that affects individuals in all demographics. The processes that occur during traumatic brain injury and neuroinflammation cannot be fully explained in most clinical and preclinical researches.Neuroinflammation is a very complex interaction between the cells of the innate and adaptive immune systems. The development of reactions of the innate immune system occurs under the influence of various signals that are released from damaged cells and tissues. This leads to the activation of neutrophils, microglia and astrocytes, the release of complement, as well as the release of histamine by mast cells.Subsequently, activation of an adaptive immune response leads to the development of later effects of neuroinflammation. The topic of biomarkers in traumatic brain injury is extensive and rapidly developing. We presented an overview of the most common and well-studied biomarkers in the literature regarding head injury in humans and their role in predicting the outcome in traumatic brain injury. Among the presented biomarkers, the most specific for traumatic brain injury are interleukins-6, -8, -10 and matrix metalloproteinases. We can use interleukin-6 to predict the outcome and risk of complications of traumatic brain injury. The concentration of interleukin-8 shows the relationship of the biomarker with mortality. We can use interleukin-10 to confirm the results of computed tomography in traumatic brain injury. Matrix metalloproteinases present the degree of violation of the blood-brain barrier and brain dysfunction. Other indicators need a more complete study to clarify their role in this pathology. Of course, for a more reliable conclusion about the patient›s condition, it is preferable to use the data of several biomarkers at the same time.

The article present the results of a study of the diagnostic efficacy of various SIR indicators (IL-6, IL-8, IL-10, TNFa, CRP), duration of dialysis before renal transplantation, post-allotransplantation period and HLA mismatch score (the number of mismatches from 6 antigens HLA loci A, B, DR) with respect to the development of chronic renal allograft dysfunction (CRAD). It was shown that the level of proinflamma-tory cytokine TNFa is a promising marker for the prognosis of the CRAD development.

Abstract. Fourteen groups of patients have been investigated and divided into 2 classes. The first class included the following cohorts of patients: relatively healthy persons, age 18 to 55 yrs (n = 50); elderly persons 60 yrs old, as well as senior persons (n = 22); persons with chronic adnexitis, women in their 1st trimester of pregnancy (n = 16); climacteric syndrome (n = 16); autoimmune thyroiditis (n = 29). The second class of patients included following cohorts: elderly persons with chronic cardiac insufficiency (CCI) II-III stage (n=49); valvular cardiac disease (rheumatism, n = 15); psoriatic arthritis (n = 12); reactive arthritis (n = 17); antiphospholipid syndrome, a sub-group in the 1st trimester of pregnancy (n = 5); systemic lupus erythematosus (n=49); decompensated atherosclerosis of femoral artery (n = 38); end-stage renal disease (n = 42). Plasma cytokines (TNFαα, IL-6, IL-8, IL-10), acute-phase C-reactive protein (CRP), cortisol, troponin I, myoglobin, D-dimers, interleukin-2 soluble receptor (IL-2sR), and eosinophil cationic protein (ECP) were determined in all the patients, by means of immune chemiluminescent technique (Immulite; Siemens Medical Solutions Diagnostics, USA). The integral indices of systemic inflammatory reaction (SIR) have been calculated, i.e., a Reactivity Coefficient (RC) and a Reactivity Level (RL). In the patients belonging to Class 1 cohorts, an absence of chronic systemic inflammation features was revealed, despite of some signs of systemic inflammatory response. Meanwhile, a majority of Class 2 patients have shown the signs of chronic systemic inflammation stage I to III.

THE AIM. Comparative analysis of the manifestations of chronic systemic inflammation (CSI) and MIA-syndrome (malnutrition-inflammation-atherosclerosis syndrome) in patients with end stage renal disease (ESRD). PATIENTS AND METHODS . The study included 40 patients with ESRD with and without MIA-syndrome and two control groups (50 and 22 people respectively). The presence of MIA-syndrome, determined based on levels of serum albumin and body mass index. As indicators CSI measured serum levels of C-reactive protein, interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF α ), soluble IL-2 receptor, eosinophil cationic protein, D-dimers, cortisol, myoglobin, troponin, calculated integral indicators of systemic inflammatory response (coefficient and the level of reactivity). RESULTS. It was revealed that the ESRD, regardless of nosology of this condition is characterized by the development of a model of the pathological process - CSI. The absence of statistically significant differences for most parameters CSI of patients with absence and presence of MIA-syndrome questions the fact of the greater severity of the typical model of the pathological process in the latter. In favor of this is the evidence of the lack of correlation between markers MIA-syndrome and indicators CSI. CONCLUSION. ESRD is characterized by the development of a model of the pathological process – chronic systemic inflammation, the mechanisms which contribute to the manifestation of some specific features MIA-syndrome.

THE AIM. Comparative analysis of the manifestations of chronic systemic inflammation (CSI) and MIA syndrome (malnutrition inflammation atherosclerosis syndrome) in patients with end stage renal disease (ESRD). PATIENTS AND METHODS. The study included 40 patients with ESRD with and without MIA syndrome and two control groups (50 and 22 people respectively). The presence of MIA syndrome, determined based on levels of serum albumin and body mass index. As indicators CSI measured serum levels of C reactive protein, interleukin (IL) 6, IL 8, IL 10, tumor necrosis factor (TNFα), soluble IL 2 receptor, eosinophil cationic protein, D dimers, cortisol, myoglobin, troponin, calculated integral indicators of systemic inflammatory response (coefficient and the level of reactivity). RESULTS. It was revealed that the ESRD, regardless of nosology of this condition is characterized by the development of a model of the pathological process CSI. The absence of statistically significant differences for most parameters CSI of patients with absence and presence of MIA syndrome questions the fact of the greater severity of the typical model of the pathological process in the latter. In favor of this is the evidence of the lack of correlation between markers MIA syndrome and indicators CSI. CONCLUSION. ESRD is characterized by the development of a model of the pathological process – chronic systemic inflammation, the mechanisms which contribute to the manifestation of some specific features MIA syndrome.

Agaricus blazei: Murill used for treatment tissue inflammation in alternative medicine was selected for immunopharmacologica1 activity test.The effects of 4-Hydroxy-17-methylincisterol (4-HM; C 21 H 33 O 3 ; M.W. 333) isolated from A. blazei on human peripheral blood mononuclear cells (PBMC) proliferation were determined by tritiated thymidine uptake.The results showed that 4-HM suppressed PBMC proliferation stimulation with phytohemagglutinin (PHA) with an IC 50 3.16 mM.Cell cycle analysis indicated that 4-HM arrested the cell cycle progression of activated PBMC from the G1 transition to the S phase.In an attempt to localize the point in the cell cycle where arrest occurred, a set of key regulatory events including gene expression of interleukin-2 (IL-2), interferon-g (IFN-g) and cyclins, activation of NF-AT, NF-kB, and Ca 2+ mobilization was examined.4-HM suppressed, in activated PBMC, the production and mRNA expression of IL-2 and IFN-g in a dose-dependent manner.Levels of cyclin protein in activated PBMC were reduced by 4-HM.The data indicated that 4-HM blocked NF-kB and NF-AT translocation in PBMC activated with PHA.The Ca 2+ mobilization in PHA treated PBMC was decreased by 4-HM.Thus, the suppressant effects of 4-HM on proliferation of PBMC activated by PHA appeared to be mediated, at least in part, through inhibition of Ca 2+ mobilization, NF-AT, and NF-kB activation, early transcripts of PBMC, especially those of important cytokines, IL-2, IFN-g, and cyclins, and arresting cell cycle progression in the cells.We predict that 4-HM may be an immunomodulator.

Study goal: to assess expression of particular and integral indices of systemic inflammation reaction in patients with end-stage renal disease (ESRD) receiving replacement therapy by haemodialysis. Material and methods: 42 patients with ESRD caused by chronic glomerulonephritis (n=22), chronic pyelonephritis (n=12) and diabetic nephropathy (n=8) were studied. All patients received replacement treatment by programmed haemodialysis for 12 hours per week. Control group 68 healthy persons (18-84 years). Levels of CRP, IL-6, IL-8, IL-10, TNF-ƒ in blood plasma were measured before and after haemodialysis by the immunochemiluminescent method (Immulite, «SIEMENS», USA). Results: In patients with ESRD an acute phase response and hypercytokinemia (most of all due to TNF-ƒ and IL-8) was noted. Its rate was reduced due to haemodialysis. Integral indices of cytokinemia (reactivity coefficient and level of reactivity RC and RL) are the most informative characteristics of the systemic inflammatory reaction. Conclusion: The phenomenon of the systemic inflammatory reaction plays a significant role in the pathogenesis of ESRD; the rate of the systemic inflammation reaction can be measured by using the integrated indices of cytokinemia.

THE AIM . Comparative analysis of the manifestations of chronic systemic inflammation (CSI) and MIA-syndrome (malnutrition-inflammation-atherosclerosis syndrome) in patients with end stage renal disease (ESRD). PATIENTS AND METHODS. The study included 40 patients with ESRD with and without MIA-syndrome and two control groups (50 and 22 people respectively). The presence of MIA-syndrome, determined based on levels of serum albumin and body mass index. As indicators CSI measured serum levels of C-reactive protein, interleukin (IL)-6, IL-8, IL-10, tumor necrosis factor (TNFα), soluble IL-2 receptor, eosinophil cationic protein, D-dimers, cortisol, myoglobin, troponin, calculated integral indicators of systemic inflammatory response (coefficient and the level of reactivity). RESULTS . It was revealed that the ESRD, regardless of nosology of this condition is characterized by the development of a model of the pathological process - CSI. The absence of statistically significant differences for most parameters CSI of patients with absence and presence of MIA-syndrome questions the fact of the greater severity of the typical model of the pathological process in the latter. In favor of this is the evidence of the lack of correlation between markers MIA-syndrome and indicators CSI. CONCLUSION . ESRD is characterized by the development of a model of the pathological process – chronic systemic inflammation, the mechanisms which contribute to the manifestation of some specific features MIA-syndrome.

Purpose of the study: to assess expression of particular and integral indicators of the systemic inflammatory reaction in patients with end-stage renal disease (ESRD) who receive replacement treatment by haemodialysis. Material and methods: 42 patients with ESRD caused by chronic glomerulonephritis (n=22), chronic pyelonephritis (n=12) and diabetic nephropathy (n=8) were studied. All patients received replacement treatment by programmed haemodialysis for 12 hours per week. Control group 68 healthy persons (18-84 years). Levels of CRP, IL-6, IL-8, IL-10, TNF-ƒ in blood plasma were measured before and after haemodialysis by immunochemiluminescent method (Immulite, «SIEMENS», USA). Results: In patients with ESRD an acute phase response and hypercytokinemia (most of all due to TNF-ƒ and IL-8) the rate of which reduced after haemodialysis were detected. Integral indices of cytokinemia (reactivity coefficient and level of reactivity RC and RL) are the most informative characteristics of systemic inflammatory reaction. Conclusion: The phenomenon of systemic inflammatory reaction plays a significant role in the pathogenesis of ESRD; the rate of the systemic inflammation reaction can be measured using the integrated indices of cytokinemia.