Aged IRF3-KO Mice are Protected from Sepsis

Goswami, Dinesh G.; Walker, Wendy E.

doi:10.2147/jir.s335203

Cited by 4 publications

(3 citation statements)

References 66 publications

(127 reference statements)

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“…Aged mice exhibit differences in the local cytokine response to sepsis, an impeded ability to return to immune homeostasis after sepsis, an altered metabolomic response, and increased vascular oxidative damage, endothelial dysfunction and coagulopathy: all of these alterations likely contribute to the age-related exacerbation of sepsis outcomes (see Supplemental Table 3). Further supporting this notion, our own recent report showed that aged C57BL/6 mice exhibited a 90% mortality rate 20 when subject to the same sepsis model described here. Please note that we did not include those aged animals in the current analysis.…”

Section: Discussionsupporting

confidence: 86%

“…This mirrors the findings reported in our recent report on aged mice. 20 However, even with the large number of animals included in our cohort, the independent effect of animal sex on sepsis mortality was not statistically significant. In addition to considering the overall effects of sex, the phenotype of female mice could potentially vary according to the estrus cycle.…”

Section: Discussionmentioning

confidence: 67%

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Common Variables That Influence Sepsis Mortality in Mice

Garcia¹,

Singh²,

Mireles³

et al. 2023

JIR

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Sepsis is characterized by a dysregulated host immune response to infection, leading to organ dysfunction and a high risk of death. The cecal ligation and puncture (CLP) mouse model is commonly used to study sepsis, but animal mortality rates vary between different studies. Technical factors and animal characteristics may affect this model in unanticipated ways, and if unaccounted for, may lead to serious biases in study findings. We sought to evaluate whether mouse sex, age, weight, surgeon, season of experiments, and timing of antibiotic administration influenced mortality in the CLP model. Methods: We created a comprehensive dataset of C57BL/6J mice that had undergone CLP surgery within our lab during years 2015-2020 from published and unpublished studies. The primary outcome was defined as the time from sepsis induction to death or termination of study (14 days). The Log rank test and Cox regression models were used to analyze the dataset. The study included 119 mice, of which 43% were female, with an average age of 12.6 weeks, an average weight of 25.3 g. 38 (32%) of the animals died. Results: In the unadjusted analyses, experiments performed in the summer and higher weight predicted a higher risk of mortality. In the stratified Cox model by sex, summer season (adjusted hazard ratio [aHR]=5.61, p=0.004) and delayed antibiotic administration (aHR=1.46, p=0.029) were associated with mortality in males, whereas higher weight (aHR=1.52, p=0.005) significantly affected mortality in females. In addition, delayed antibiotic administration (HR=1.42, p=0.025) was associated with mortality in the nonsummer seasons, but not in the summer season. Discussion: In conclusion, some factors specific to sex and season have a significant influence on sepsis mortality in the CLP model. Consideration of these factors along with appropriate group matching or adjusted analysis is critical to minimize variability beyond the experimental conditions within a study.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 67%

Common Variables That Influence Sepsis Mortality in Mice

Garcia¹,

Singh²,

Mireles³

et al. 2023

JIR

Self Cite

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“…Sepsis is a serious, life-threatening syndrome that is one of the leading causes of death in hospitals. 1 , 2 Sepsis was also among the leading causes of the death associated with COVID-19. 3 Despite significant advances in critical care, sepsis still has a relatively high short-term mortality rate due to organ failure due to a dysregulated response to infection.…”

Section: Introductionmentioning

confidence: 99%

Establishment and Effectiveness Evaluation of a Scoring System-RAAS (RDW, AGE, APACHE II, SOFA) for Sepsis by a Retrospective Analysis

Huang¹,

Jiang²,

Li³

et al. 2022

JIR

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Chromatin-Associated Molecular Patterns (CAMPs) in sepsis

2022

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Several molecular patterns have been identified that recognize pattern recognition receptors. Pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) are commonly used terminologies to classify molecules originating from pathogen and endogenous molecules, respectively, to heighten the immune response in sepsis. Herein, we focus on a subgroup of endogenous molecules that may be detected as foreign and similarly trigger immune signaling pathways. These chromatin-associated molecules, i.e., chromatin containing nuclear DNA and histones, extracellular RNA, mitochondrial DNA, telomeric repeat-containing RNA, DNA- or RNA-binding proteins, and extracellular traps, may be newly classified as chromatin-associated molecular patterns (CAMPs). Herein, we review the release of CAMPs from cells, their mechanism of action and downstream immune signaling pathways, and targeted therapeutic approaches to mitigate inflammation and tissue injury in inflammation and sepsis.

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Aged IRF3-KO Mice are Protected from Sepsis

Cited by 4 publications

References 66 publications

Common Variables That Influence Sepsis Mortality in Mice

Common Variables That Influence Sepsis Mortality in Mice

Establishment and Effectiveness Evaluation of a Scoring System-RAAS (RDW, AGE, APACHE II, SOFA) for Sepsis by a Retrospective Analysis

Chromatin-Associated Molecular Patterns (CAMPs) in sepsis

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