Rethinking the concept of sepsis and septic shock

Cabrita, Joana A.; Pinheiro, Isabel; Falcão, Luiz Menezes

doi:10.1016/j.ejim.2018.06.002

Cited by 18 publications

(17 citation statements)

References 21 publications

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“…Endotoxic shock is a complex disorder that develops because of dysregulated host response to an infection and it has been widely regarded as a major global health problem (33, 34). In the case of endotoxic shock, inflammatory mediators are produced in excess, resulting in hemodynamic instability and multiple organ failure (35).…”

Section: Discussionmentioning

confidence: 99%

Leukadherin-1-Mediated Activation of CD11b Inhibits LPS-Induced Pro-inflammatory Response in Macrophages and Protects Mice Against Endotoxic Shock by Blocking LPS-TLR4 Interaction

et al. 2019

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Dysregulation of macrophage has been demonstrated to contribute to aberrant immune responses and inflammatory diseases. CD11b, expressed on macrophages, plays a critical role in regulating pathogen recognition, phagocytosis, and cell survival. In the present study, we explored the effect of leukadherin-1 (LA1), an agonist of CD11b, on regulating LPS-induced pro-inflammatory response in macrophages and endotoxic shock. Intriguingly, we found that LA1 could significantly reduce mortalities of mice and alleviated pathological injury of liver and lung in endotoxic shock. In vivo studies showed that LA1-induced activation of CD11b significantly inhibited the LPS-induced pro-inflammatory response in macrophages of mice. Moreover, LA1-induced activation of CD11b significantly inhibited LPS/IFN-γ-induced pro-inflammatory response in macrophages by inhibiting MAPKs and NF-κB signaling pathways in vitro . Furthermore, the mice injected with LA1-treated BMDMs showed fewer pathological lesions than those injected with vehicle-treated BMDMs in endotoxic shock. In addition, we found that activation of TLR4 by LPS could endocytose CD11b and activation of CD11b by LA1 could endocytose TLR4 in vitro and in vivo , subsequently blocking the binding of LPS with TLR4. Based on these findings, we concluded that LA1-induced activation of CD11b negatively regulates LPS-induced pro-inflammatory response in macrophages and subsequently protects mice from endotoxin shock by partially blocking LPS-TLR4 interaction. Our study provides a new insight into the role of CD11b in the pathogenesis of inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Leukadherin-1-Mediated Activation of CD11b Inhibits LPS-Induced Pro-inflammatory Response in Macrophages and Protects Mice Against Endotoxic Shock by Blocking LPS-TLR4 Interaction

et al. 2019

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“…It should be noted that currently no set of biomarkers can reliably detect the presence of sepsis in a child, and PERSEVERE panels require special equipment and are aimed only at recognizing septic shock in ICU conditions, so the use of laboratory studies should always be based on the clinical picture (58,59).…”

Section: Specific Diagnosis Of Sepsis and Septic Shock In Childrenmentioning

confidence: 99%

Modern Diagnostics of Sepsis and Septic Shock in Children

et al. 2020

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Sepsis is still one of the leading causes of child mortality worldwide, despite advances in its diagnosis and treatment. Difficulties in recognizing the transition of a localized infectious-inflammatory process to a generalized one lead to a belated diagnosis and the beginning of therapy. Meanwhile, the earlier treatment is started, the higher the patients' chances of life. Early diagnosis of sepsis, which corresponds to modern ideas about this condition, is one of the main tasks for both scientists and practitioners. The aim of this review is to study modern recommendations for the diagnosis of sepsis and septic shock in children. The article reflects the epidemiology, etiological features, modern definitions and methods of diagnosis of pediatric sepsis.

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“…An early diagnosis should be the goal in management of SIRS patients, allowing starting adequate treatment in an early stage …”

Section: Introductionmentioning

confidence: 99%

“…13 An early diagnosis should be the goal in management of SIRS patients, allowing starting adequate treatment in an early stage. 14,15 Our aim was to compare PON-1 activity in sick horses classified as SIRS-positive or SIRS-negative, as proposed by others, 16 and to investigate the performances of PON-1 activity in terms of sensitivity, specificity, and likelihood ratio in identifying SIRS-positive and negative horses.…”

Section: Introductionmentioning

confidence: 99%

Paraoxonase‐1 activity evaluation as a diagnostic and prognostic marker in horses and foals

Ruggerone

Paltrinieri

Giordano

et al. 2020

Veterinary Internal Medicne

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Background In several species, paraoxonase‐1 (PON‐1) decreases during inflammation, because of the presence of oxidative stress; its measurement recently has been validated in horses, but its role as a clinical biomarker is unknown. Objectives To evaluate sensitivity, specificity and likelihood ratio of PON‐1 activity to identify systemic inflammatory response syndrome (SIRS)‐positive horses or horses with a poor prognosis. Animals One hundred seventy‐two blood samples from 58 sick horses from 3 different veterinary hospitals. Methods In a cross‐sectional study, PON‐1 activity was measured upon admission and at 24‐hour intervals until discharge or death, and results were analyzed based on SIRS status and outcome. Results No statistically significant difference was found in median PON‐1 activity between SIRS and non‐SIRS cases or between survivors and non‐survivors except for mares, in which PON‐1 activity was significantly lower in SIRS‐positive horses (P = .05). The sensitivity of PON‐1 activity in identifying horses with SIRS or negative outcome was low (0.0%‐46.2% depending on the examined group) but its specificity was high (87.0%‐100.0%). However, when PON‐1 is low, the likelihood of death is 2.40‐3.89 times higher than the likelihood of survival. Repeated measurement of PON‐1 after treatment does not predict outcome. Conclusions and Clinical Importance Evaluation of PON‐1 activity in horses with inflammation might be advisable in the future, but only low activity at admission may be relevant in predicting SIRS or negative outcome.

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Rethinking the concept of sepsis and septic shock

Cited by 18 publications

References 21 publications

Leukadherin-1-Mediated Activation of CD11b Inhibits LPS-Induced Pro-inflammatory Response in Macrophages and Protects Mice Against Endotoxic Shock by Blocking LPS-TLR4 Interaction

Leukadherin-1-Mediated Activation of CD11b Inhibits LPS-Induced Pro-inflammatory Response in Macrophages and Protects Mice Against Endotoxic Shock by Blocking LPS-TLR4 Interaction

Modern Diagnostics of Sepsis and Septic Shock in Children

Paraoxonase‐1 activity evaluation as a diagnostic and prognostic marker in horses and foals

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