Sepsis and septic shock

Cecconi, Maurizio; Evans, Laura; Levy, Mitchell M.; Rhodes, Andrew

doi:10.1016/s0140-6736(18)30696-2

Cited by 1,298 publications

(928 citation statements)

References 141 publications

Supporting

Mentioning

878

Contrasting

Unclassified

Order By: Relevance

“…Sepsis causes a major systemic inflammatory state that is part of the physiological reaction to infection. However, this inflammatory response can also be uncontrolled, causing excessive or unbalanced production of inflammatory cytokines [4], potentially resulting in organ dysfunction and death. Furthermore, prolonged production of anti-inflammatory mediators may lead to a profound immunosuppression state, sometimes named immunoparalysis, during which most of the sepsis-associated mortality is observed [5].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

oXiris® Use in Septic Shock: Experience of Two French Centres

et al. 2019

View full text Add to dashboard Cite

Background: Sepsis is a dysregulated host response to an infection and can result in organ dysfunctions and death. Extracorporeal blood purification techniques aim to improve the prognosis of these patients by modulating the unbalanced immune response. This study reports our experience with the use of the oXiris® membrane for septic shock patients requiring continuous renal replacement therapy (CRRT). Summary: Thirty-one patients were diagnosed with septic shock and underwent CRRT with the oXiris® membrane between 2014 and 2019. We compared the observed hospital mortality with that predicted by the Simplified Acute Physiology Score II (SAPS II). Change in the Sequential Organ Failure Assessment (SOFA) score and of the main clinical and biological parameters over time were analyzed. Hospital mortality was lower than predicted for the most severe patients (60 vs. 91% for the [74–87] SAPS II quartile and 70 vs. 98% for the [87–163] SAPS II quartile, p < 0.02). There was no significant improvement in the SOFA score from 0h to 48 h. An 88% relative decrease in norepinephrine infusion was observed (median at 0 h was 1.69 [0.52–2.45] µg/kg/min; at 48 h it was 0.20 [0.09–1.14] µg/kg/min, p = 0.002). Lactataemia and pH were significantly improved over time. Patients with intra-abdominal sepsis as well as those with Gram-negative bacilli (GNB) infections seemed to benefit the most from the therapy. Key Messages: CRRT with the oXiris® haemofilter resulted in higher observed survival than predicted by a severity score (SAPS II) for the most severe patients. Haemodynamic status and lactataemia appeared to improve, especially in intra-abdominal sepsis and GNB infections.

show abstract

Section: Discussionmentioning

confidence: 99%

“…It is now widely accepted that pathogen-associated molecular patterns, such as endotoxins that are recognized by the host immune system, cause a significant increase in pro-and anti-inflammatory cytokines [4]. This cytokine storm in the acute phase of sepsis is responsible for shock, organ failure and secondary immunoparalysis [5].…”

Section: Introductionmentioning

confidence: 99%

oXiris® Use in Septic Shock: Experience of Two French Centres

et al. 2019

View full text Add to dashboard Cite

show abstract

“…[17][18][19][20][21][22][23][24] It is well known that Tregs play a critical role in regulating immune homeostasis, including several pathological conditions such as allergic lung inflammation, autoimmune diseases, transplant rejection and tolerance. [17][18][19][20][21][22][23][24] It is well known that Tregs play a critical role in regulating immune homeostasis, including several pathological conditions such as allergic lung inflammation, autoimmune diseases, transplant rejection and tolerance.…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐38 protects against sepsis by augmenting immunosuppressive activity of CD4⁺CD25⁺ regulatory T cells

Huang

et al. 2019

J Cellular Molecular Medi

View full text Add to dashboard Cite

| INTRODUC TI ONCD4 + CD25 + regulatory T cells (Tregs) can regulate host responses to infections and tumours, and contribute to the prevention of allergies, autoimmune diseases and transplant rejection. 1-4 CD4 + CD25 + Tregs are essential for maintenance of immune homeostasis and self-tolerance. They express several crucial molecular markers, including cytotoxic T lymphocyte-associated antigen 4 (CTLA-4, also termed CD152), glucocorticoid-induced tumour necrosis factor receptor (GITR) and forkhead/winged helix transcription factor p3 (Foxp3).Knockdown of these factors leads to lethal lymphoproliferative phenotypes. 5-8 Concomitantly, CD4 + CD25 + Tregs can produce various potent anti-inflammatory cytokines, such as interleukin (IL)-10 and transforming growth factor (TGF)-β, which cause immunosuppression of effector T cells. 9-12 Moreover, CD4 + CD25 + Tregs can reduce IL-2 production and inhibit polyclonal T cell activity in vitro, 13 and Abstract Naturally occurring CD4 + CD25 + regulatory T cells (Tregs) are required to limit immune-induced pathology and to maintain homeostasis during the early-phase of sepsis. This study aimed to investigate the role of interleukin (IL)-38, a newly described member of the IL-1 cytokine family, in mediated immune response of CD4 + CD25 + Tregs in sepsis. Here, we provide evidence that expressions of IL-38 and its receptor were detected in murine CD4 + CD25 + Tregs. Stimulation of CD4 + CD25 + Tregs with LPS markedly up-regulated the expression of IL-38. Treatment with rmIL-38 dramatically enhanced the immunosuppressive activity of CD4 + CD25 + Tregs after LPS stimulation and in septic mice induced by CLP, resulting in amplification of helper T cell (Th) 2 response and reduction in the proliferation of effector T cells. These effects were robustly abrogated when anti-IL-38 antibody was administered. Administration of rmIL-38 improved the survival rate of CLP mice. In addition, CD4 + CD25 + Tregs depletion before the onset of sepsis obviously abolished IL-38-mediated protective response. These findings suggest that IL-38 enhances the immunosuppressive activity of CD4 + CD25 + Tregs, which might contribute to the improvement of host immune function and prognosis in the setting of sepsis. K E Y W O R D Simmune response, interleukin-38, regulatory T cells, sepsis

show abstract

“…1,7 The excessive inflammatory response characterized by systemic inflammatory response syndrome is correlated with sepsis. 1,7 The excessive inflammatory response characterized by systemic inflammatory response syndrome is correlated with sepsis.…”

Section: Discussionmentioning

confidence: 99%

“…Sepsisassociated multiple organ dysfunction syndrome and septic shock severely reduce the survival of patients [1][2][3] ; the mortality rate for multiple organ dysfunction syndrome is between 25% and 30%, and the mortality rate increases to 40% for septic shock. Sepsisassociated multiple organ dysfunction syndrome and septic shock severely reduce the survival of patients [1][2][3] ; the mortality rate for multiple organ dysfunction syndrome is between 25% and 30%, and the mortality rate increases to 40% for septic shock.…”

Section: Introductionmentioning

confidence: 99%

ING4 alleviated lipopolysaccharide‐induced inflammation by regulating the NF‐κB pathway via a direct interaction with SIRT1

Yang

et al. 2020

Immunol Cell Biol

View full text Add to dashboard Cite

Sepsis is a complex inflammatory disorder in which high mortality is associated with an excessive inflammatory response. Inhibitor of growth 4 (ING4), which is a cofactor of histone acetyltransferase and histone deacetylase complexes, could negatively regulate this inflammation. However, the exact molecular signaling pathway regulated by ING4 remains uncertain. As a pivotal histone deacetylase, Sirtuin1 (SIRT1), which is widely accepted to be an antiinflammatory molecule, has not been found to be linked to ING4. This study investigated how ING4 is involved in the regulation of inflammation by constructing lipopolysaccharide (LPS)-induced macrophage and mouse sepsis models. Our results revealed that ING4 expression decreased, whereas the levels of proinflammatory cytokines increased in LPS-stimulated cultured primary macrophages and RAW 264.7 cells. ING4 transfection was confirmed to alleviate the LPS-induced upregulation of proinflammatory cytokine expression both in vitro and in vivo. In addition, ING4-overexpressing mice were hyposensitive to an LPS challenge and displayed reduced organ injury. Furthermore, immunoprecipitation indicated a direct interaction between ING4 and the SIRT1 protein. Moreover, ING4 could block nuclear factor-kappa B (NF-jB) P65 nuclear translocation and restrict P65 acetylation at lysine 310 induced by LPS treatment. These results are the first to clarify that the antiinflammatory role of ING4 is associated with SIRT1, through which ING4 inhibits NF-jB signaling activation. Our studies provide a novel signaling axis involving ING4/SIRT1/NF-jB in LPS-induced sepsis.

show abstract

Sepsis and septic shock

Cited by 1,298 publications

References 141 publications

oXiris® Use in Septic Shock: Experience of Two French Centres

oXiris® Use in Septic Shock: Experience of Two French Centres

Interleukin‐38 protects against sepsis by augmenting immunosuppressive activity of CD4⁺CD25⁺ regulatory T cells

ING4 alleviated lipopolysaccharide‐induced inflammation by regulating the NF‐κB pathway via a direct interaction with SIRT1

Contact Info

Product

Resources

About

Sepsis and septic shock

Cited by 1,298 publications

References 141 publications

oXiris® Use in Septic Shock: Experience of Two French Centres

oXiris® Use in Septic Shock: Experience of Two French Centres

Interleukin‐38 protects against sepsis by augmenting immunosuppressive activity of CD4+CD25+ regulatory T cells

ING4 alleviated lipopolysaccharide‐induced inflammation by regulating the NF‐κB pathway via a direct interaction with SIRT1

Contact Info

Product

Resources

About

Interleukin‐38 protects against sepsis by augmenting immunosuppressive activity of CD4⁺CD25⁺ regulatory T cells