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A pairwise cytokine code explains the organism-wide response to sepsis

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE224146 | GEO | 2024/01/08

REPOSITORIES: GEO

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A pairwise cytokine code explains the organism-wide response to sepsis [Whole-tissue RNA-seq]

Project description:Sepsis is a systemic response to infection with life-threatening consequences. Our understanding of the molecular and cellular impact of sepsis across organs remains rudimentary. Here, we characterize the pathogenesis of sepsis by measuring dynamic changes in gene expression across organs. To pinpoint molecules controlling organ states in sepsis, we compare the effects of sepsis on organ gene expression to those of 6 singles and 15 pairs of recombinant cytokines. Strikingly, we find that the pairwise effects of tumor necrosis factor plus interleukin (IL)-18, interferon-gamma or IL-1 suffice to mirror the impact of sepsis across tissues. Mechanistically, we map the cellular effects of sepsis and cytokines by computing changes in the abundance of 195 cell types across 9 organs, which we validate by whole-mouse spatial profiling. Our work decodes the cytokine cacophony in sepsis into a pairwise cytokine message capturing the gene, cell and tissue responses of the host to the disease.

2024-01-08 | GSE224127 | GEO

A pairwise cytokine code explains the organism-wide response to sepsis [spatial transcriptomics by Visium]

2024-01-08 | GSE224145 | GEO

A pairwise cytokine code explains the organism-wide response to sepsis

Project description:A pairwise cytokine code explains the organism-wide response to sepsis

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A pairwise cytokine code explains the organism-wide response to sepsis [Spatial transcriptomics by Array-seq]

2024-01-08 | GSE248904 | GEO

A pairwise cytokine code explains the organism-wide response to sepsis [spatial transcriptomics by Visium]

Project description:A pairwise cytokine code explains the organism-wide response to sepsis [spatial transcriptomics by Visium]

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A pairwise cytokine code explains the organism-wide response to sepsis [Whole-tissue RNA-seq]

Project description:A pairwise cytokine code explains the organism-wide response to sepsis [Whole-tissue RNA-seq]

| PRJNA929947 | ENA

A pairwise cytokine code explains the organism-wide response to sepsis [Spatial transcriptomics by Array-seq]

Project description:A pairwise cytokine code explains the organism-wide response to sepsis [Spatial transcriptomics by Array-seq]

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Organism-Wide Analysis of Sepsis Reveals Mechanisms of Systemic Inflammation

Project description:Phospholipase A2 group V (PLA2G5) is a secretory and Ca2+-dependent lipolytic enzyme and is inducible during several pathologic conditions. However, it has been unknown how PLA2G5 plays a role in sepsis. To study the role of PLA2G5 in sepsis, we performed lipidomics analysis of plasma and tissues from LPS-injected mice with or without PLA2G5 blockade. Here, we showed that PLA2G5 is involved in the production of fatty acids such as oleic acid and linoleic acid, lysophospholipids such as lysophosphatidic acid, lysophosphatidylcholine, lysophatidylethanolamine, and lysophosphatidylserine species, and metabolites derived from polyunsaturated fatty acids such as arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid, and linoleic acids during sepsis. Thus, PLA2G5 regulates selective lipid pathways during sepsis.

2023-01-23 | ST002455 | MetabolomicsWorkbench

Dynamic and integrated transcriptional code orchestrates the angiogenic response

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-03-28 | GSE109626 | GEO

Corticosteroids in Sepsis and Septic Shock: A Systematic Review, Pairwise, and Dose-Response Meta-Analysis.

Project description:ObjectivesTo perform a systematic review and meta-analysis to assess the efficacy and safety of corticosteroids in patients with sepsis.Data sourcesWe searched PubMed, Embase, and the Cochrane Library, up to January 10, 2023.Study selectionWe included randomized controlled trials (RCTs) comparing corticosteroids with placebo or standard care with sepsis.Data extractionThe critical outcomes of interest included mortality, shock reversal, length of stay in the ICU, and adverse events.Data analysisWe performed both a pairwise and dose-response meta-analysis to evaluate the effect of different corticosteroid doses on outcomes. We used Grading of Recommendations Assessment, Development and Evaluation to assess certainty in pooled estimates.Data synthesisWe included 45 RCTs involving 9563 patients. Corticosteroids probably reduce short-term mortality (risk ratio [RR], 0.93; 95% CI, 0.88-0.99; moderate certainty) and increase shock reversal at 7 days (RR, 1.24; 95% CI, 1.11-1.38; high certainty). Corticosteroids may have no important effect on duration of ICU stay (mean difference, -0.6 fewer days; 95% CI, 1.48 fewer to 0.27 more; low certainty); however, probably increase the risk of hyperglycemia (RR, 1.13; 95% CI, 1.08-1.18; moderate certainty) and hypernatremia (RR, 1.64; 95% CI, 1.32-2.03; moderate certainty) and may increase the risk of neuromuscular weakness (RR, 1.21; 95% CI, 1.01-1.45; low certainty). The dose-response analysis showed a reduction in mortality with corticosteroids with optimal dosing of approximately 260 mg/d of hydrocortisone (RR, 0.90; 95% CI, 0.83-0.98) or equivalent.ConclusionsWe found that corticosteroids may reduce mortality and increase shock reversal but they may also increase the risk of hyperglycemia, hypernatremia, and neuromuscular weakness. The dose-response analysis indicates optimal dosing is around 260 mg/d of hydrocortisone or equivalent.

| S-EPMC10798738 | biostudies-literature

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