During Sepsis and COVID-19, the Pro-Inflammatory and Anti-Inflammatory Responses Are Concomitant

Cavaillon, Jean‐Marc

doi:10.1007/s12016-023-08965-1

Cited by 10 publications

(4 citation statements)

References 66 publications

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“…Current research supports the notion that both SIRS and CARS occur simultaneously at the onset of sepsis ( 36 , 37 ). However, an imbalance in the intensity and duration of responses between these two phases leads to clinical manifestations characterized initially by an excessive inflammatory response and later by immune suppression or immune paralysis.…”

Section: Sepsis-induced Immunological Dysregulationsupporting

confidence: 81%

Immunotherapy in the context of sepsis-induced immunological dysregulation

Wu,

Wang,

et al. 2024

Front. Immunol.

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Sepsis is a clinical syndrome caused by uncontrollable immune dysregulation triggered by pathogen infection, characterized by high incidence, mortality rates, and disease burden. Current treatments primarily focus on symptomatic relief, lacking specific therapeutic interventions. The core mechanism of sepsis is believed to be an imbalance in the host’s immune response, characterized by early excessive inflammation followed by late immune suppression, triggered by pathogen invasion. This suggests that we can develop immunotherapeutic treatment strategies by targeting and modulating the components and immunological functions of the host’s innate and adaptive immune systems. Therefore, this paper reviews the mechanisms of immune dysregulation in sepsis and, based on this foundation, discusses the current state of immunotherapy applications in sepsis animal models and clinical trials.

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Section: Sepsis-induced Immunological Dysregulationsupporting

confidence: 81%

Immunotherapy in the context of sepsis-induced immunological dysregulation

Wu,

Wang,

et al. 2024

Front. Immunol.

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“…Among the host determinants, the innate immune system is vital for prompt recognition and elimination of pathogens. Nevertheless, in sepsis, the innate immune response may be hyperactive or hypoactive, resulting in a cytokine storm or immunosuppression, respectively [ 39 , 40 ]. In addition, the immune dysregulation can trigger a cascade of events including impairment in cellular metabolism [ 17 , 41 , 42 ].…”

Section: Discussionmentioning

confidence: 99%

New insights into the role of mitochondrial metabolic dysregulation and immune infiltration in septic cardiomyopathy by integrated bioinformatics analysis and experimental validation

Li,

Yu,

et al. 2024

Cell Mol Biol Lett

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Background Septic cardiomyopathy (SCM), a common cardiovascular comorbidity of sepsis, has emerged among the leading causes of death in patients with sepsis. SCM’s pathogenesis is strongly affected by mitochondrial metabolic dysregulation and immune infiltration disorder. However, the specific mechanisms and their intricate interactions in SCM remain unclear. This study employed bioinformatics analysis and drug discovery approaches to identify the regulatory molecules, distinct functions, and underlying interactions of mitochondrial metabolism and immune microenvironment, along with potential interventional strategies in SCM. Methods GSE79962, GSE171546, and GSE167363 datasets were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and module genes were identified using Limma and Weighted Correlation Network Analysis (WGCNA), followed by functional enrichment analysis. Machine learning algorithms, including support vector machine–recursive feature elimination (SVM–RFE), least absolute shrinkage and selection operator (LASSO) regression, and random forest, were used to screen mitochondria-related hub genes for early diagnosis of SCM. Subsequently, a nomogram was developed based on six hub genes. The immunological landscape was evaluated by single-sample gene set enrichment analysis (ssGSEA). We also explored the expression pattern of hub genes and distribution of mitochondria/inflammation-related pathways in UMAP plots of single-cell dataset. Potential drugs were explored using the Drug Signatures Database (DSigDB). In vivo and in vitro experiments were performed to validate the pathogenetic mechanism of SCM and the therapeutic efficacy of candidate drugs. Results Six hub mitochondria-related DEGs [MitoDEGs; translocase of inner mitochondrial membrane domain-containing 1 (TIMMDC1), mitochondrial ribosomal protein S31 (MRPS31), F-box only protein 7 (FBXO7), phosphatidylglycerophosphate synthase 1 (PGS1), LYR motif containing 7 (LYRM7), and mitochondrial chaperone BCS1 (BCS1L)] were identified. The diagnostic nomogram model based on the six hub genes demonstrated high reliability and validity in both the training and validation sets. The immunological microenvironment differed between SCM and control groups. The Spearman correlation analysis revealed that hub MitoDEGs were significantly associated with the infiltration of immune cells. Upregulated hub genes showed remarkably high expression in the naive/memory B cell, CD14+ monocyte, and plasma cell subgroup, evidenced by the feature plot. The distribution of mitochondria/inflammation-related pathways varied across subgroups among control and SCM individuals. Metformin was predicted to be the most promising drug with the highest combined score. Its efficacy in restoring mitochondrial function and suppressing inflammatory responses has also been validated. Conclusions This study presents a comprehensive mitochondrial metabolism and immune infiltration landscape in SCM, providing a potential novel direction for the pathogenesis and medical intervention of SCM.

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Section: Introductionmentioning

confidence: 99%

“…This phenomenon is known as Compensatory Anti-Inflammatory Response Syndrome (CARS) (Figure 1) [11]. However, recent studies have shown that during the early stages of sepsis, both pro-inflammatory and anti-inflammatory responses occur simultaneously [12]. Existing meta-analysis has shown that the neutrophil-to-lymphocyte ratio may be a useful prognostic biomarker for patients with sepsis [13].…”

Section: Introductionmentioning

confidence: 99%

The Changes in the Quantity of Lymphocyte Subpopulations during the Process of Sepsis

Yang,

Zhu,

Feng

2024

IJMS

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Sepsis remains a global challenge, especially in low- and middle-income countries, where there is an urgent need for easily accessible and cost-effective biomarkers to predict the occurrence and prognosis of sepsis. Lymphocyte counts are easy to measure clinically, and a large body of animal and clinical research has shown that lymphocyte counts are closely related to the incidence and prognosis of sepsis. This review extensively collected experimental articles related to lymphocyte counts since the unification of the definition of sepsis. The article categorizes and discusses the relationship between absolute lymphocyte counts, intrinsic lymphocyte subsets, effector T-lymphocytes, B-lymphocytes, dendritic cells, and the incidence and prognosis of sepsis. The results indicate that comparisons of absolute lymphocyte counts alone are meaningless. However, in addition to absolute lymphocyte counts, innate lymphocyte subsets, effector T-cells, B-lymphocytes, and dendritic cells have shown certain research value in related studies.

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During Sepsis and COVID-19, the Pro-Inflammatory and Anti-Inflammatory Responses Are Concomitant

Cited by 10 publications

References 66 publications

Immunotherapy in the context of sepsis-induced immunological dysregulation

Immunotherapy in the context of sepsis-induced immunological dysregulation

New insights into the role of mitochondrial metabolic dysregulation and immune infiltration in septic cardiomyopathy by integrated bioinformatics analysis and experimental validation

The Changes in the Quantity of Lymphocyte Subpopulations during the Process of Sepsis

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