Severity Of Systemic Inflammatory Response Research Articles

Potential for infusion correction of COVID-19-associated endotheliopathy

To evaluate the relationship between the systemic inflammatory response and the severity of COVID-19-associated endotheliopathy and the effect of succinate-containing crystalloid solution (sodium meglumine succinate) on it in patients with severe COVID-19. Clinical and laboratory parameters of 53 intensive care unit's patients with COVID-19 complicated by community-acquired bilateral multisegmental pneumonia were analyzed. Intensive therapy complex of 27 patients (study group) included daily infusion of 1.5% solution of sodium meglumine succinate (Reamberin) in the daily dose of 10 ml/kg for at least 11 days (or during the whole stay in the unit). A similar volume of Ringer's solution was present in the control group of 26 patients. The levels of endotheliocytosis, homocysteine, and systemic inflammatory response were determined at all stages of the study. The evaluation of endotheliopathy degree in the meglumine succinate group showed a significant reduction of initially elevated levels of endotheliemia and homocysteinemia at all study stages. The pattern of changes in the study group was highly correlated (r=0.90-0.96) with the dynamics of systemic inflammatory response parameters-fibrinogenemia, C-reactive protein and interleukin-6 levels. As normalization of the immune imbalance, we regarded the termination of lymphopenia in the Reamberin group. Early inclusion of Reamberin infusion into intensive therapy of severe COVID-19, in comparison with Ringer's solution, leads to significant and stable correction of the severity of systemic inflammatory response, which in turn is naturally reflected in the severity of endothelial dysfunction, multiple organ failure, and also leads to a decrease in 28-day mortality.

Paracrine effects of stem cell conditioned medium on production of oxygen reactive species in blood neutrophils in acetaminophen-induced liver failure

The current study examined the effects of mesenchymal stem cells-derived conditioned medium on the severity of systemic inflammatory response induced by the administration of acetaminophen, as well as its long-term effects on hepatic tissues. A conditioned medium fraction ˂30 кDа showed maximum protective effect. Proteins of this fraction reduce the degree of systemic inflammatory response and liver tissue fibrosis long after the toxin administration. Liver tissues from experimental animals were examined, and a correlation between the reduction of granulocytic infiltration scoring and the degree hepatic parenchymal necrosis was demonstrated (confirmed by the cytolytic enzyme level). The ˂30 кDа fraction increased the spontaneous but decreased phobrol-12-myristate-13-acetate-induced intracellular production of reactive oxygen species. Results from this study show that the level of macrophage migration inhibitory factor and expression of thioredoxin significantly increase as compared to controls during increased spontaneous production of reactive oxygen species in neutrophils.

The problem of non-alcoholic fatty liver disease, metabolic syndrome and atherosclerosis: from the unity of pathogenesis to the possibility of ursodeoxycholic acid correction

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver pathologies, the prevalence of which is steadily increasing worldwide. Cardiovascular disease (CVD) is another group of common diseases that have similar pathophysiological mechanisms with NAFLD. CVD and NAFLD occur against the background of metabolic syndrome, systemic insulin resistance, oxidative stress, altered lipid metabolism. The course of both diseases predisposes to the development of endothelial dysfunction and formation/instability of atherosclerotic plaques. The progression of NAFLD is associated with an increase of the thickness of intima-media complex and calcification of coronary arteries, which is accompanied by an increased risk of subclinical and clinically significant atherosclerosis development. Patients with NAFLD have a high cardiovascular risk, the maximum increase of which should be expected in patients with severe fibrosis (F3–F4 on the NAFLD Fibrosis Score scale). Ursodeoxycholic acid reduces the severity of systemic inflammatory response and oxidative stress, improves lipid metabolism, increases the hypolipidemic effect of statins, reduces the degree of hyperglycemia and insulin resistance, inhibits the formation of atherosclerotic plaques, has vasodilating effect. The presence of significant pleiotropic properties in combination with apparent cytoprotective, choleretic, antiapoptic, anticholestatic, immunomodulatory activity allows to include ursodeoxycholic acid in NAFLD treatment, non-alcoholic steatohepatitis in order to reduce the clinical manifestations of atherosclerosis and prevent CVD progression.

IMMUNOLOGICAL MARKERS OF LONG-TERM EFFECTS OF TREATMENT IN PATIENTS WITH MILD COGNITIVE IMPAIRMENT

The goal of this research was to study the clinical efficacy of course-based neurotrophic therapy in mild cognitive impairment (MCI) and the effect of therapy on immune parameters in patients, and to assess the prognostic value of the dynamics of immune parameters during the year after treatment. 20 patients with MCI receiving intravenous Cerebrolysin (20 infusions of 30 ml with increasing dose during the first four days) were examined. Neuropsychological and immunological examination was carried out immediately before the study, after 3 months., 6 months and after 1 year after the end of treatment. It was found that after therapy, patients had a long-term decrease in the severity of systemic inflammatory response, and that marked signs of systemic inflammation at the beginning of follow-up combined with a persistent decrease in the level of immunoglobulin G in dynamics were prognostic markers of MCI progression. In conclusion, it wass shown that neurotrophic therapy has a good clinical effect and has a favorable immunomodulatory effect in aMCI, and the relationship between the dynamics of humoral immunity and systemic inflammation and the risk of progression of cognitive impairment in patients within 1 year after therapy was established.

Features of the cytokine balance in infectious hemorrhagic colitis in children

The aim of the study was to study the features of cytokine balance and their effect on clinical and laboratory parameters in infectious hemorrhagic colitis in children. Materials and methods. In the Department of intestinal infections in 2018 observed 28 children with infectious haemorrhagic colitis. The diagnosis was established taking into account clinical recommendations; the severity of the disease was determined by the Clark index; the etiology was verified according to bacteriological and molecular studies of feces, serological methods. In the acute period of the disease, the concentration of cytokines in the blood serum — TNF-a, IL-4, IL-6, IL-10 was studied by enzyme immunoassay. Mann-Whitney method, Kruskal-Wallis dispersion analysis, Pearson correlation method we used to estimate the obtained data.Results. The age structure of patients was dominated by young children (53.6%). Mild form of the disease was diagnosed in 32.1% of patients, moderate — in 67.9%. A high level of IL-4 was observed against a relatively low level of TNF-a, IL-6 and IL-10. Significantly higher concentrations of TNF-a and IL-6 were found in children with moderate form of the disease. The maximum values of IL-6 were observed in young children, IL-10 — in infants. In the moderate form of the disease, negative correlations of IL-4 with the number of leukocytes (r = –0.46; p = 0.05) and platelets (r = –0.48; p < 0.05) in the hemogram noted. Early age patients were found to have correlations of TNF-a with the relative number of rod neutrophils (r = 0.62; p < 0.01). There was a significant correlation of IL-4 with the relative number of segmental neutrophils (r = 0.49; p < 0.05). The relationship of TNF-a with the severity of the disease (r = 0.42; p < 0.05) revealed. The data on the possible suppressive effect of TNF-a and IL-10 on the synthesis of urea and the relationship of IL-6 with reactive changes in the liver obtained.Conclusion. Studies of cytokine balance in infectious hemorrhagic colitis in children showed the severity of systemic inflammatory response with the activation of Th-2 immune response. The correlation of TNF-a with the severity of the disease was established, which may have diagnostic and prognostic value.

Sex differences of inflammation in target organs, induced intraperitoneal injection of lipopolysaccharide, depend on its dose

PurposeThe aim of our research was to study sex differences and the severity of inflammatory changes in target organs and the peculiarities of immunological disorders when low and high doses of lipopolysaccharide (LPS) were administered to rats.MethodsMale and female 2- to 3-month-old Wistar rats (200–250 g) were injected intraperitoneally with Escherichia coli LPS in one of two doses: 1.5 or 15 mg/kg. In a day after the LPS injection, we studied endotoxin, corticosterone, sex steroids, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activity levels in the serum; morphological disorders in the lung, liver, thymus, and spleen; ex vivo production of IL-2, IL-4, tumor necrosis factor (TNF), and interferon γ (IFNγ) by splenic cells activated by ConA; and relative amount of T- and B-lymphocytes in the peripheral blood.ResultsAfter the injection of low-dose LPS, the serum endotoxin level increased only in males and was combined with a more pronounced inflammatory response in the lungs and thymus and an increase in ALT and AST activity levels without any changes in corticosterone level. After the injection of high-dose LPS, the inflammatory and pathological changes in the target organs manifested as severe endotoxemia and sex differences of pathological changes in the lungs and liver were not revealed. The level of production of IL-2, IL-4, IFNγ, and TNF by splenic cells and the number of T-lymphocytes, including cytotoxic cells, in the peripheral blood, decreased in males, which is an evidence of a pronounced suppression of the immune response.ConclusionWe have shown that the morphofunctional changes in the organs of the immune system in females and males, as well as the intensity of the sex differences of inflammation, depend on the severity of systemic inflammatory response, induced by different doses of LPS.

Glucoseinsulin Mixture as a Cardioprotective Agent in Cardiology and Cardiac Surgery (Review)

The literature review presents an analysis of publications describing the use of a glucose%insulin mixture as a cardioprotective agent in acute myocardial infarction and in cardiac surgeries with extracorporeal circulation (ECC). It summarizes historical aspects of implementation of the glucose%insulin therapy in cardiology and car% diac surgery. Possible mechanisms of action of the glucose-insulin-potassium mixture in acute ischemia and myocardial infarction were analyzed (normalization of electrical processes on the cardiomyocyte membrane, replenishment of metabolic substrates and increased production rate of adenosine triphosphoric acid due to glycolysis, decreased intensity of non%esterified fatty acid oxidation, decreased apoptosis, etc.). It discusses results of clinical studies evaluating prescription of the mixture for acute myocardial infarction, including data from metaanalyses. It demonstrated that the role and the clinical efficacy of the preventive and therapeutic measure under consideration in acute myocardial infarction are still the subject of discussion and require further research. It also analyzed modern concepts explaining the cardioprotective effects of insulin and glucose during surgeries with ECC (decreased insulin resistance, activation of anaplerosis, stimulation of intracellular signaling pathways maintaining the viability of cells, reduction of the severity of systemic inflammatory response, immunomodulating effect, etc.). Review discusses results of clinical studies including data from randomized clinical trials and metaanalyses performed over the last 5 years that demonstrated the absence of the effect of the glucose%insulin therapy on the hospital mortality. Various studies demonstrated its positive effects including decreased incidence of peri% operative myocardial infarctions and intensity of inotropic support, increased values of postoperative cardiac index, decreased duration of postoperative mechanical ventilation and ICU stay, etc. Review concludes that the interest to the therapeutic and preventive use of the glucose%-nsulin mixture in both emergency cardiology and cardiac surgery has been revived recently.

Effect of Statins on Development of Early Cognitive Dysfunction After Coronary Artery Bypass Grafting

We studied the effect of rosuvastatin on the development of early postoperative cognitive dysfunction (POCD) in patients after coronary artery bypass grafting (CABG). One hundred nine men aged 45-70 year was divided into two groups. Group 1 comprised 69 patients (mean age 56.8 ± 5.2 years) who were given 20 mg of rosuvastatin for 10-14 days before CABG and until discharge. Patients of group 2 (n=40, mean age 55.9 ± 5.3 years) did not take rosuvastatin. It was shown that patients of group 2 had better neuropsychological parameters after CABG in comparison with the patients of group 2. Patients of group 1 had lower concentrations of interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor α, high sensitivity C reactive protein, and higher concentrations of IL-10. Group 2 patients had worse neuropsychological parameters which were associated with higher concentrations of proinflammatory cytokines. These results may indicate that preoperative therapy with rosuvastatin had decreased the severity of systemic inflammatory response and reduced the development of early POCD after CABG.

Correlation of magnesium deficiency with C-reactive protein in elective cardiac surgery with cardiopulmonary bypass for ischemic heart disease

Background and objectiveCardiac surgery is associated with systemic inflammatory response, which is triggered by cardiopulmonary bypass (CPB) and possibly with underlying magnesium deficiency. Animal studies have shown that magnesium deficiency intensifies oxidative stress and inflammatory processes. We aimed to find a link between serum, erythrocyte, cardiac tissue magnesium concentration and C-reactive protein (CRP) as an inflammatory marker in patients undergoing elective cardiac surgery with CPB. Materials and methodsThe data of 27 patients undergoing elective cardiac surgery with CPB for ischemic heart disease were analyzed. Measurements were taken at the baseline, i.e., 24h before surgery (serum magnesium, CRP); time point 1, before CPB (serum, erythrocyte and cardiac tissue magnesium); time point 2, after CPB (serum, erythrocyte and cardiac tissue magnesium), and time point 3, 15–17h after surgery (serum, erythrocyte magnesium, CRP). ResultsThere was a negative correlation between baseline serum magnesium and baseline CRP (P=0.009; r=−0.492), negative correlation between cardiac tissue magnesium at the time point 1 and baseline CRP (P=0.021; r=−0.443), and positive correlation between CRP at time point 3 and erythrocyte magnesium at time point 2 (P<0.001; r=0.637). ConclusionsThe data of our study verify that inflammatory marker CRP and magnesium concentration in serum and cardiac tissue before the surgery are inversely related in patients undergoing elective cardiac surgery with CPB. Well-planned further studies are needed to evaluate the importance of underlying magnesium deficiency on the severity of systemic inflammatory response and postoperative complications after surgery with CPB.

Histologic and Immunohistochemical Features Associated with Outcome in Neonatal Necrotizing Enterocolitis

The aim of the study was to compare histopathologic and immunohistochemical markers between survivors and nonsurvivors of surgical necrotizing enterocolitis (NEC). With appropriate ethical approval, archived resection specimens were identified for patients with NEC (Bell Stages II and III) for whom outcome data (survival yes/no) were available. For each specimen, a severely affected part of the bowel and the least affected area, usually the margin, were analyzed. Histologic findings were scored as no necrosis/mucosal necrosis/full-thickness necrosis and immunohistochemistry staining for inflammatory markers vascular cell adhesion protein (VCAM), CD68, CD20, intercellular adhesion molecule (ICAM), human leukocyte antigen (HLA-DR), CD3, Cleaved Caspase-3 (CC3), forkhead box P3 (FOXP3), CD62p, and C4d were performed and scored on a semiquantitative scale (0; no staining to 10, strong extensive staining). All samples were identified by only their study number throughout and the samples were analyzed completely blinded to all clinical information. Data were compared using chi-square test for trend (histologic data) or Mann-Whitney U test. A total of 123 slides from 60 patients (birth weight 1.3 ± 0.1 kg, gestational age at birth 29.3 ± 0.6 weeks) were examined. Seventy-four specimens (60%) were from survivors and 49 specimens (40%) were from those who subsequently died. There was no relationship between histologic severity of necrosis (none/mucosal/full thickness) and mortality (p = 0.58). VCAM (adhesion molecule; p = 0.005) and CC3 (a marker of apoptosis, p = 0.008) expression was significantly elevated in nonsurvivors, whereas there were no differences in CD68, CD20, ICAM, HLA-DR, CD3, FOXP3, CD62p, or C4d expression. There is a poor relationship between histologic severity of bowel necrosis and patient survival in infants undergoing bowel resection for NEC. There is statistically increased expression of VCAM reflecting severity of systemic inflammatory response and evidence of increased apoptosis in the form of CC3 expression in those who subsequently die, but no histologic features can predict outcome.

Systemic inflammatory response syndrome as a predictor of anastomotic leakage after esophagectomy

Esophageal anastomotic leakage is still a major cause of morbidity and mortality after esophagectomy. We conducted this study to elucidate how anastomotic leakage affects the systemic inflammatory response syndrome (SIRS) criteria. The subjects of this retrospective study were 61 patients who underwent esophagectomy. We evaluated their preoperative status, the surgical procedures, and postoperative systemic response, including white blood cell count, heart rate, respiratory rate, body temperature, and laboratory data up to postoperative day (POD) 4. Anastomotic leakage developed in nine patients (14.8%) and was found on POD 7 on average. These patients had a significantly longer hospital stay than those without leakage. Although no difference was observed in postoperative changes of any of the SIRS criteria, the postoperative incidence of SIRS was significantly higher in the patients with anastomotic leakage on POD 4. The number of positive criteria for SIRS was also significantly higher in patients with anastomotic leakage than in those without leakage on PODs 3 and 4. The SIRS scoring system is valuable for evaluating the severity of systemic inflammatory response caused by anastomosis leakage, and may serve as an indicator for prompt management.

Systemic Consequences of Oxidative Stress following Aortic Surgery Correlate with the Degree of Antioxidant Defenses

The purpose of this study was to correlate the preoperative level of antioxidant defenses, measured by the plasma total antioxidant capacity (TAC), to the degree of postoperative systemic inflammatory response, measured by the severity of pulmonary injury following elective aortic surgery. Twenty-four patients had TAC measured preoperatively and 24 hr postoperatively. Chest radiography and arterial blood gases were obtained preoperatively and serially during the first 24 hr after surgery. Using objective radiologic criteria and blood gas analysis, the degree of pulmonary edema and pulmonary dysfunction were quantified. All patients showed evidence of pulmonary dysfunction in the first 24 hr following surgery. Fifteen of the 24 patients showed radiographic evidence of noncardiogenic pulmonary edema in the immediate postoperative period. In this group, the TAC was lower than in those without pulmonary edema immediately following surgery (p = 0.03). Preoperative TAC was associated with the degree of pulmonary edema in the postoperative period (r = -0.372, p = 0.067). These results suggest that preoperative antioxidant supplementation may favorably impact the severity of systemic inflammatory response following ischemia and reperfusion injury.