scholarly journals Receptors, Mediators, and Mechanisms Involved in Bacterial Sepsis and Septic Shock

2003 ◽  
Vol 16 (3) ◽  
pp. 379-414 ◽  
Author(s):  
Edwin S. Van Amersfoort ◽  
Theo J. C. Van Berkel ◽  
Johan Kuiper
Keyword(s):  
Septic Shock ◽  
Mononuclear Cells ◽  
Lipoteichoic Acid ◽  
The Body ◽  
Plasma Lipoproteins ◽  
Bacterial Sepsis ◽  
Proinflammatory Mediators ◽  
Sepsis And Septic Shock ◽  
Bacterial Constituents

SUMMARY Bacterial sepsis and septic shock result from the overproduction of inflammatory mediators as a consequence of the interaction of the immune system with bacteria and bacterial wall constituents in the body. Bacterial cell wall constituents such as lipopolysaccharide, peptidoglycans, and lipoteichoic acid are particularly responsible for the deleterious effects of bacteria. These constituents interact in the body with a large number of proteins and receptors, and this interaction determines the eventual inflammatory effect of the compounds. Within the circulation bacterial constituents interact with proteins such as plasma lipoproteins and lipopolysaccharide binding protein. The interaction of the bacterial constituents with receptors on the surface of mononuclear cells is mainly responsible for the induction of proinflammatory mediators by the bacterial constituents. The role of individual receptors such as the toll-like receptors and CD14 in the induction of proinflammatory cytokines and adhesion molecules is discussed in detail. In addition, the roles of a number of other receptors that bind bacterial compounds such as scavenger receptors and their modulating role in inflammation are described. Finally, the therapies for the treatment of bacterial sepsis and septic shock are discussed in relation to the action of the aforementioned receptors and proteins.

The Role of Histones and Heparin in Sepsis: A Review

2021 ◽  
pp. 088506662199232
Author(s):  
Xiaojuan Zhang ◽  
Xin Li
Keyword(s):  
Septic Shock ◽  
Multiple Organ ◽  
Clinical Settings ◽  
The Past ◽  
Life Saving ◽  
Extracellular Histones ◽  
Sepsis And Septic Shock ◽  
Development And Management ◽  
Made In

Septic shock with multiple organ failure is a devastating situation in clinical settings. Through the past decades, much progress has been made in the management of sepsis and its underlying pathogenesis, but a highly effective therapeutic has not been developed. Recently, macromolecules such as histones have been targeted in the treatment of sepsis. Histones primarily function as chromosomal organizers to pack DNA and regulate its transcription through epigenetic mechanisms. However, a growing body of research has shown that histone family members can also exert cellular toxicity once they relocate from the nucleus into the extracellular space. Heparin, a commonly used anti-coagulant, has been shown to possess life-saving capabilities for septic patients, but the potential interplay between heparin and extracellular histones has not been investigated. In this review, we summarize the pathogenic roles of extracellular histones and the therapeutic roles of heparin in the development and management of sepsis and septic shock.

scholarly journals Plasma interleukin-6 levels correlate with survival in patients with bacterial sepsis and septic shock

2021 ◽  
Vol 11 (4) ◽  
pp. 224-230
Author(s):  
Monica Chavez Vivas ◽  
Hector Fabio Villamarin Guerrero ◽  
Antonio Jose Tascon ◽  
Augusto Valderrama-Aguirre
Keyword(s):  
Septic Shock ◽  
Cox Regression ◽  
Serum Levels ◽  
Significant Decline ◽  
Bacterial Sepsis ◽  
Inflammatory Biomarker ◽  
Statistical Program ◽  
Sepsis And Septic Shock ◽  
Time Of Admission ◽  
Admission Variables

AbstractIn this study, IL-6 levels were assessed as inflammatory biomarker of bacterial sepsis in patients hospitalized at the ICU of the hospital of Colombia.Materials and methodsProspective study on 62 patients diagnosed with sepsis and septic shock. An ELISA assay was used to test serum levels of IL-6 at admission and 48 h after admission. Variables were analyzed by χ2 test (alfa <0.05). Multivariable Cox regression was used to determine the survival with the statistical program SPSS v23.00.ResultsPatient's median age was 53 years old and 59.7% were male. Lung was the most common primary site of infection (43.5%), and hypertension comorbidity with higher prevalence (40%). Infection by Gram negative bacteria were significantly more frequent among patients than Gram positive (P = 0.037). Overall, survival analysis showed that 10 (16.1%) patients died with a survival median of 7.00 +4.874 (2–3) days. In patients with sepsis we detected a significant decline in the average of IL-6 serum levels after 48 h of admission [7.50 (SD: 7.00–68.00) pg/mL vs. 68.00 [SD: 7.00–300.00] pg/mL (P = 0.000). Only 25% of patients with septic shock who presented high levels of IL-6 at the time of admission and at 48 h had a survival up to 15 days (P = 0.005).ConclusionWe found significant differences between the plasma levels of IL-6 during the first 48 h after admission to the ICU among patients with sepsis and septic shock. Patients with sepsis had a significant decline in IL-6 levels, whereas in patients who developed septic shock, levels of this cytokine remained high and have a lower survival compared to those who maintained low levels of IL-6.

scholarly journals The Role of Serum Procalcitonin in Predicting Bacterial Sepsis in Patients With Hypothyroidism

2019 ◽  
Vol 104 (12) ◽  
pp. 5915-5922
Author(s):  
Aditya S Shirali ◽  
James X Wu ◽  
Catherine Y Zhu ◽  
Alfonso Ocampo ◽  
Chi-Hong Tseng ◽  
...  
Keyword(s):  
Septic Shock ◽  
Test Performance ◽  
Serum Levels ◽  
Primary Hypothyroidism ◽  
Bacterial Sepsis ◽  
Thyroid C Cells ◽  
Failure Assessment ◽  
History Of ◽  
Sepsis And Septic Shock ◽  
Design And Methods

Abstract Context Serum levels of procalcitonin (PCT), a protein produced by the thyroid C cells under physiologic conditions, are high during sepsis. Objective To assess the test performance of serum PCT in predicting bacterial sepsis and septic shock in patients with hypothyroidism compared with those who have euthyroidism. Design and Methods This retrospective study evaluated patients with no history of thyroid dysfunction (euthyroid), primary hypothyroidism [medical hypothyroidism (MH)], and postsurgical hypothyroidism from total thyroidectomy (TT) identified from a prospectively maintained database who had PCT testing from 2005 to 2018. Quick Sequential Organ Failure Assessment score ≥ 2 or positive bacterial cultures identified bacterial sepsis, and a mean arterial pressure less than 65 mm Hg or a vasopressor requirement defined septic shock. Sensitivity and specificity of PCT for evaluation of bacterial sepsis and septic shock were measured. Results We identified 217 euthyroid patients, 197 patients with MH, and 84 patients with TT. Bacterial sepsis was found in 98 (45.2%), 92 (46.7%), and 36 (42.9%) of these patients, respectively (P > 0.05). Septic shock was identified in 13 (6.0%), 13 (6.6%), and 5 (6.0%) patients (P > 0.05), respectively. With use of a PCT cutoff of 0.5 µg/L for bacterial sepsis, the sensitivity was 59%, 61%, and 53% (P > 0.05) and specificity was 81%, 77%, and 81% (P > 0.05) for the diagnosis of bacterial sepsis in euthyroid, MH, and TT patients, respectively. With use of a PCT cutoff of 2.0 µg/L for septic shock, the sensitivity was 46%, 62%, and 63% (P > 0.05) and specificity was 86%, 82%, and 91% (P > 0.05) for the diagnosis of septic shock in these patients, respectively. Conclusions Despite the thyroidal origin of PCT, hypothyroidism did not affect the diagnostic performance of serum PCT levels in predicting bacterial sepsis or septic shock.

NF-κB activation as a pathological mechanism of septic shock and inflammation

2006 ◽  
Vol 290 (4) ◽  
pp. L622-L645 ◽  
Author(s):  
Shu Fang Liu ◽  
Asrar B. Malik
Keyword(s):  
Septic Shock ◽  
Human Subjects ◽  
Myocardial Dysfunction ◽  
Multiple Organ ◽  
Organ Injury ◽  
Pathological Mechanism ◽  
Proinflammatory Gene ◽  
Intensive Investigation ◽  
Sepsis And Septic Shock

The pathophysiology of sepsis and septic shock involves complex cytokine and inflammatory mediator networks. NF-κB activation is a central event leading to the activation of these networks. The role of NF-κB in septic pathophysiology and the signal transduction pathways leading to NF-κB activation during sepsis have been an area of intensive investigation. NF-κB is activated by a variety of pathogens known to cause septic shock syndrome. NF-κB activity is markedly increased in every organ studied, both in animal models of septic shock and in human subjects with sepsis. Greater levels of NF-κB activity are associated with a higher rate of mortality and worse clinical outcome. NF-κB mediates the transcription of exceptional large number of genes, the products of which are known to play important roles in septic pathophysiology. Mice deficient in those NF-κB-dependent genes are resistant to the development of septic shock and to septic lethality. More importantly, blockade of NF-κB pathway corrects septic abnormalities. Inhibition of NF-κB activation restores systemic hypotension, ameliorates septic myocardial dysfunction and vascular derangement, inhibits multiple proinflammatory gene expression, diminishes intravascular coagulation, reduces tissue neutrophil influx, and prevents microvascular endothelial leakage. Inhibition of NF-κB activation prevents multiple organ injury and improves survival in rodent models of septic shock. Thus NF-κB activation plays a central role in the pathophysiology of septic shock.

scholarly journals Interplay between Nox2 Activity and Platelet Activation in Patients with Sepsis and Septic Shock: A Prospective Study

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Giusy Tiseo ◽  
Elena Cavarretta ◽  
Arianna Forniti ◽  
Cristina Nocella ◽  
Sebastiano Sciarretta ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Septic Shock ◽  
Platelet Aggregation ◽  
Platelet Activation ◽  
Healthy Controls ◽  
Sample Collection ◽  
Oxidative Stress Status ◽  
Sepsis And Septic Shock ◽  
A Prospective Study

Background. Although preclinical studies highlighted the potential role of NADPH oxidase (NOX) in sepsis, only few studies evaluated the oxidative stress in patients with sepsis and septic shock. The objective of the study is to appraise the oxidative stress status and platelet function in patients with sepsis and septic shock compared to healthy controls. Methods and Results. Patients with sepsis or septic shock admitted to the hospital Policlinico Umberto I (Sapienza University, Rome) underwent a blood sample collection within 1 hour from admission. Platelet aggregation, serum thromboxane B2 (TxB2), soluble NOX2-derived peptides (sNox2-dp), and hydrogen peroxide breakdown activity (HBA) were measured and compared to those of healthy volunteers. Overall, 33 patients were enrolled; of these, 20 (60.6%) had sepsis and 13 (39.4%) septic shock. Compared to healthy controls ( n = 10 , age 67.8 ± 3.2 , male 50%), patients with sepsis and septic shock had higher platelet aggregation (49% (IQR 45-55), 60% (55.75-67.25), and 73% (IQR 69-80), respectively, p < 0.001 ), higher serum TxB2 (77.5 (56.5-86.25), 122.5 (114-131.5), and 210 (195-230) pmol/L, respectively, p < 0.001 ), higher sNox2-dp (10 (7.75-12), 19.5 (17.25-21), and 33 (29.5-39) pg/mL, respectively, p < 0.001 ), and lower HBA (75% (67.25-81.5), 50% (45-54.75), and 27% (21.5-32.5), respectively, p < 0.001 ). Although not statistically significant, a trend in higher levels of serum TxB2 and sNox2-dp in patients who died was observed. Conclusions. Patients with septic shock exhibit higher Nox2 activity and platelet activation than patients with sepsis. These insights joined to better knowledge of these mechanisms could guide the identification of future prognostic biomarkers and new therapeutic strategies in the scenario of septic shock.

scholarly journals Interleukin-6 kinetics can be useful for early treatment monitoring of severe bacterial sepsis and septic shock

2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Thomas Klag ◽  
Giulio Cantara ◽  
Udo Sechtem ◽  
Anastasios Athanasiadis
Keyword(s):  
Septic Shock ◽  
Interleukin 6 ◽  
Early Treatment ◽  
Treatment Monitoring ◽  
Bacterial Sepsis ◽  
Case Histories ◽  
Sepsis And Septic Shock ◽  
Kinetics Of

Early appropriate anti-microbial therapy is necessary to improve outcomes of septic patients. We describe 20 case histories of patients with severe bacterial sepsis regarding kinetics of several biomarkers. We found that interleukin-6 is able to predict survival and might be able to evaluate appropriateness of anti-microbial therapy.

scholarly journals Toll-like receptor pathway signaling is differently regulated in neurophils and peripheral mononuclear cells of patients with sepsis, severe sepsis and septic shock

Critical Care ◽  
2008 ◽  
Vol 12 (Suppl 5) ◽  
pp. P45
Author(s):  
Reinaldo Salomão ◽  
Milena Brunialti ◽  
Natalia Gomes ◽  
Marialice Mendes ◽  
Ricardo Diaz ◽  
...  
Keyword(s):  
Septic Shock ◽  
Severe Sepsis ◽  
Mononuclear Cells ◽  
Toll Like Receptor ◽  
Peripheral Mononuclear Cells ◽  
Sepsis And Septic Shock
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