Enhancing Recovery From Sepsis

Prescott, Hallie C.; Angus, Derek C.

doi:10.1001/jama.2017.17687

Cited by 628 publications

(582 citation statements)

References 95 publications

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“…[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

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| 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

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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

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“…With an incidence rate of 270 per 100,000 person-years [1], sepsis is common and often fatal with hospital mortality of 26% [1]. Half of patients recover, but among those who survive sepsis, one-sixth have permanent organ damage [2], cognitive impairment, and physical disability [3]. The number of sepsis patients who survive intensive care is growing due to a rise in the incidence of sepsis [1,4], a general increase in the number and use of intensive care unit (ICU) beds [5], as well as progress in the treatment of sepsis [6].…”

Section: Introductionmentioning

confidence: 99%

What matters most to sepsis survivors: a qualitative analysis to identify specific health-related quality of life domains

et al. 2018

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Purpose It is unknown how sepsis survivors conceptualize health-related quality of life (HRQL). We aimed to identify important HRQL domains for this population. Methods A literature search was performed to inform an interview guide. Open-ended interviews were held with 15 purposefully sampled sepsis survivors. Interview transcripts were analyzed by interpretative phenomenological analysis to allow themes to develop organically. Resulting codes were reviewed by an independent expert. The preliminary list of domains was rated in a two-round Delphi consensus procedure with therapists and survivors. Results Eleven domains emerged as critically important: Psychological impairment, Fatigue, Physical impairment, Coping with daily life, Return to normal living, Ability to walk, Cognitive impairment, Self-perception, Control over one’s life, Family support and Delivery of health care. Sepsis survivors want a “normal life”, to walk again, to regain control without cognitive impairment. Family support is essential to overcome sepsis aftermaths. Conclusions Survivors described many HRQL domains which are not captured by the QoL instruments that have traditionally been used to study ICU survivorship (i.e. SF-36 and EQ-5D). Future studies of QoL in ICU survivors should consider using both a traditional instrument so that results are comparable to previous research, as well as a more holistic QoL measurement instrument like the WHOQOL-BREF.

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“…Sepsis is defined as life‐threatening organ dysfunction resulted from dysregulated host immune response and systemic inflammation to microbial infection . It is estimated to influence more than 19 million people each year globally, and the in‐hospital mortality rates are around 15%‐25% for sepsis patients . Pulmonary dysfunction such as acute respiratory distress syndrome (ARDS) is one of the predominant organ dysfunctions caused by systemic inflammation, uncontrolled cytokine, or release of other mediators, which not only contributes to the high mortality of sepsis but also reduces the quality of life for sepsis survivors .…”

Section: Introductionmentioning

confidence: 99%

Long non‐coding RNA THRIL predicts increased acute respiratory distress syndrome risk and positively correlates with disease severity, inflammation, and mortality in sepsis patients

Wang

et al. 2019

Clinical Laboratory Analysis

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BackgroundThis present study aimed to investigate the correlation of long non‐coding RNA THRIL (lnc‐THRIL) with acute respiratory distress syndrome (ARDS) risk, disease severity, inflammation, and mortality in sepsis patients.MethodsA total of 109 sepsis patients admitted to intensive care units were consecutively recruited, and their blood samples were collected. After admission, patients were supervised and screened daily to identify the occurrence of ARDS. Clinical characteristics, routine laboratory testing, and disease severity were recorded, and all enrolled patients were followed up until death in the hospital or discharge for mortality records. Lnc‐THRIL was detected by quantitative polymerase chain reaction, and inflammatory cytokine levels were measured by human enzyme‐linked immunoassay.ResultsA total of 32 (29.4%) sepsis patients occurred ARDS and 77 (71.6%) did not. Lnc‐THRIL was upregulated in ARDS group compared with non‐ARDS group, and it had good value in distinguishing ARDS from non‐ARDS in sepsis patients (AUC: 0.706; 95%CI: 0.602‐0.809). Besides, lnc‐THRIL, smoke, and chronic obstructive pulmonary disease independently predicted increased risk of ARDS. As for disease severity, lnc‐THRIL positively correlated with APACHE II score and SOFA score in sepsis patients. Regarding inflammation, lnc‐THRIL was positively associated with CRP, PCT, TNF‐α, and IL‐1β levels in sepsis patients. Additionally, the mortality rate was 30.2%, and lnc‐THRIL was upregulated in non‐survivors compared with survivors, presenting a good value (AUC: 0.780; 95%CI: 0.683‐0.876) in predicting mortality in sepsis patients.ConclusionLnc‐THRIL predicts increased risk of ARDS and positively correlates with disease severity, inflammation, and mortality in sepsis patients.

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Enhancing Recovery From Sepsis

Cited by 628 publications

References 95 publications

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

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

What matters most to sepsis survivors: a qualitative analysis to identify specific health-related quality of life domains

Long non‐coding RNA THRIL predicts increased acute respiratory distress syndrome risk and positively correlates with disease severity, inflammation, and mortality in sepsis patients

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Enhancing Recovery From Sepsis

Cited by 628 publications

References 95 publications

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

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

What matters most to sepsis survivors: a qualitative analysis to identify specific health-related quality of life domains

Long non‐coding RNA THRIL predicts increased acute respiratory distress syndrome risk and positively correlates with disease severity, inflammation, and mortality in sepsis patients

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

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