Immune Cell Number, Phenotype, and Function in the Elderly with Sepsis

He, Wanxue; Xiao, Kun; Fang, Min; Xie, Lixin

doi:10.14336/ad.2020.0627

Cited by 33 publications

(32 citation statements)

References 237 publications

(264 reference statements)

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“…Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection (1), and the intense early inflammatory response would cause massive depletion of immune cells and immune factors, which is an important cause of immune suppression in the later stages of sepsis (27). The presence of immune decline in the elderly itself, to some degree, would affect the function of all types of immune cells of the innate and adaptive immune systems, especially the progressive decline of the function of CD8 + T cells and CD4 + T cells, which would lead to a higher susceptibility to sepsis and mortality among the elderly (28). Currently, several studies have shown that MSCs can reduce the mortality and the degree of organ damage in sepsis model animals (29,30), and the results of the latest preclinical meta-analysis have shown that MSCs treatment can outstandingly reduce the mortality rate in sepsis animals.…”

Section: Discussionmentioning

confidence: 99%

The Study on the Regulation of Th Cells by Mesenchymal Stem Cells Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats

et al. 2022

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Sepsis is the leading cause of death among patients, especially elderly patients, in intensive care units worldwide. In this study, we established a sepsis model using naturally aged rats and injected 5×106 umbilical cord-derived MSCs via the tail vein. Each group of rats was analyzed for survival, examined for biochemical parameters, stained for organ histology, and analyzed for the Th cell subpopulation ratio and inflammatory cytokine levels by flow cytometry. Western blotting was performed to detect the activity of the JAK-STAT signaling pathway. We designed the vitro experiments to confirm the regulatory role of MSCs, and verified the possible mechanism using JAK/STAT inhibitors. It was revealed from the experiments that the 72 h survival rate of sepsis rats treated with MSCs was significantly increased, organ damage and inflammatory infiltration were reduced, the levels of organ damage indicators were decreased, the ratios of Th1/Th2 and Th17/Treg in peripheral blood and spleen were significantly decreased, the levels of pro-inflammatory cytokines such as IL-6 were decreased, the levels of anti-inflammatory cytokines such as IL-10 were increased, and the levels of STAT1 and STAT3 phosphorylation were reduced. These results were validated in in vitro experiments. Therefore, this study confirms that MSCs can control the inflammatory response induced by sepsis by regulating Th cells and inflammatory factors, and that this leads to the reduction of tissue damage, protection of organ functions and ultimately the improvement of survival in aged sepsis model rats. Inhibition of the JAK-STAT signaling pathway was surmised that it may be an important mechanism for their action.

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Section: Discussionmentioning

confidence: 99%

The Study on the Regulation of Th Cells by Mesenchymal Stem Cells Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats

et al. 2022

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“…Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection(1), and the intense early in ammatory response causes a massive depletion of immune cells and immune factors, which is an important cause of immune suppression in the later stages of sepsis(26). The presence of some degree of immune decline in the elderly itself affects the progressive decline in the function of all types of immune cells of the innate and adaptive immune systems, especially CD8 + T cells and CD4 + T cells, and this results in a higher susceptibility to sepsis and mortality in the elderly (27). Currently, many studies have shown that MSCs can improve mortality and the degree of organ damage in sepsis model animals(28, 29), and the results of the latest preclinical meta-analysis have shown that MSC treatment can signi cantly reduce mortality in sepsis model animals.…”

Section: Discussionmentioning

confidence: 99%

The Study on the Regulation of Th Cells by MSCs Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats

Wang

Deng

Sun

et al. 2021

Preprint

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Background: Sepsis is the leading cause of death among patients, especially elderly patients, in intensive care units worldwide. However, there is no effective treatment for sepsis in the aging population. Therefore, we designed such a study to confirm the protective effect of MSCs against sepsis in the elderly and to explore its mechanisms.Methods: In this study, we established a sepsis model using naturally aged SD rats and injected 5×106 umbilical cord-derived MSCs via the tail vein. Each group of rats was analyzed for survival, examined for biochemical parameters, stained for organ histology, and analyzed for the Th cell subpopulation ratio and inflammatory cytokine levels by flow cytometry. Western blotting was performed to detect the activity of the JAK-STAT signaling pathway. We designed in vitro experiments to confirm the regulatory role of MSCs, and verified the possible mechanism using JAK/STAT inhibitors. Results: The results revealed that the 72 h survival rate of sepsis rats treated with MSCs was significantly increased, organ damage and inflammatory infiltration were reduced, the levels of organ damage indicators were decreased, the ratios of Th1/Th2 and Th17/Treg in peripheral blood and spleen were significantly decreased, the levels of pro-inflammatory cytokines such as IL-6 were decreased, the levels of anti-inflammatory cytokines such as IL-10 were increased, and the levels of STAT1 and STAT3 phosphorylation were reduced. These results were validated in in vitro experiments. Conclusions: Therefore, this study confirms that MSCs can control the inflammatory response induced by sepsis by regulating Th cells and inflammatory factors, and that this leads to reduction of tissue damage, protection of organ functions and ultimately improvement of survival in aged sepsis model rats. Inhibition of the JAK-STAT signaling pathway may be an important mechanism for their action.

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“…All patients over 18 years who presented with severe lymphopenia (lymphocyte count ≤ 0.5 G/L) on ED admission (first blood cell count) were studied [ 9 ]. Patients with chronic hematological or oncological diseases, immunosuppression (Human Immunodeficiency Virus, transplant, treatment with steroids at any dose or immunotherapy for more than three months), hepatocellular insufficiency defined as any chronic diseases associated with an impairment of hepatocyte functions [ 13 ], and elderly patients (age > 85 years considered as having physiological immunosenescence) were excluded [ 14 – 16 ].…”

Section: Methodsmentioning

confidence: 99%

High prevalence of infections in non-COVID-19 patients admitted to the Emergency Department with severe lymphopenia

et al. 2022

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Background In the Emergency Department (ED), early and accurate recognition of infection is crucial to prompt antibiotic therapy but the initial presentation of patients is variable and poorly characterized. Lymphopenia is commonly associated with bacteraemia and poor outcome in intensive care unit patients. The objective of this retrospective study was to assess the prevalence of community-acquired infection in a cohort of unselected patients admitted to the ED with undifferentiated symptoms and severe lymphopenia. Methods This is a retrospective single-center study conducted over a 1 year-period before the COVID-19 pandemic. Consecutive adult patients admitted to the ED with severe lymphopenia (lymphocyte count < 0.5 G/L) were studied. Patients with hematological or oncological diseases, HIV infection, hepato-cellular deficiency, immunosuppression, or patients over 85 years old were excluded. Diagnoses of infection were validated by an independent adjudication committee. The association between various parameters and infection was assessed using a multivariate logistic regression analysis. Results Of 953 patients admitted to the ED with severe lymphopenia, 245 were studied (148 men; mean age: 63 ± 19 years). Infection was confirmed in 159 patients (65%) (bacterial: 60%, viral: 30%, other: 10%). Only 61 patients (25%) were referred to the ED for a suspected infection. In the univariate analysis, SIRS criteria (OR: 5.39; 95%CI: 3.04–9.70; p < 0.001) and temperature ≥ 38.3 °C (OR: 10.95; 95%CI: 5.39–22.26; p < 0.001) were strongly associate with infection. In the multivariate analysis, only SIRS criteria (OR: 2.4; 95%CI: 1.48–3.9; p < 0.01) and fever (OR: 3.35; 95%CI: 1.26–8.93; p = 0.016) were independently associated with infection. Conclusions The prevalence of underlying infection is high in patients admitted to the ED with lymphopenia, irrespective of the reason for admission. Whether lymphopenia could constitute a valuable marker of underlying infection in this clinical setting remains to be confirmed prospectively in larger cohorts. Trial registration: No registration required as this is a retrospective study.

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Immune Cell Number, Phenotype, and Function in the Elderly with Sepsis

Cited by 33 publications

References 237 publications

The Study on the Regulation of Th Cells by Mesenchymal Stem Cells Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats

The Study on the Regulation of Th Cells by Mesenchymal Stem Cells Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats

The Study on the Regulation of Th Cells by MSCs Through the JAK-STAT Signaling Pathway to Protect Naturally Aged Sepsis Model Rats

High prevalence of infections in non-COVID-19 patients admitted to the Emergency Department with severe lymphopenia

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