ArticleAlcoholism, clinical and experimental research2021
Ethanol Exposure Attenuates Immune Response in Sepsis via Sirtuin 2 Expression.
Article in Alcoholism, clinical and experimental research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers, 1 of them a synthesis that pooled it.
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Who cites it
11 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Pooled it
- SIRT2 Regulates EX VIVO PBMC Adhesion in Septic Shock Patients.Shock (Augusta, Ga.) · 2026Article
- Hyaluronan 35 prevents endotoxin-mediated dysregulated skeletal muscle proteostasis during ethanol exposure.American journal of physiology. Endocrinology and metabolism · 2026Article
- Mitoquinol improves phagocytosis and glycolysis in ethanol-exposed macrophages via HIF-1α-PFKP axis.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- INHIBITING SIRT2 ATTENUATES SEPSIS-INDUCED ACUTE KIDNEY INJURY VIA FOXO1 ACETYLATION-MEDIATED AUTOPHAGY ACTIVATION.Shock (Augusta, Ga.) · 2025Article
- Role of Myeloid Cell-Specific Adenylyl Cyclase Type 7 in Lipopolysaccharide- and Alcohol-Induced Immune Responses.International journal of molecular sciences · 2024Article
- Effect of ethanol exposure on innate immune response in sepsis.Journal of leukocyte biology · 2024Review
- Metabolic mechanisms orchestrated by Sirtuin family to modulate inflammatory responses.Frontiers in immunology · 2024Review
- Alcohol and Immunology: Mechanisms of multi-organ damage. Summary of the 2022 alcohol and Immunology research interest group (AIRIG) meeting.Alcohol (Fayetteville, N.Y.) · 2023Review
- SIRT2-PFKP interaction dysregulates phagocytosis in macrophages with acute ethanol-exposure.Frontiers in immunology · 2022Article
- SIRT2 promotes murine melanoma progression through natural killer cell inhibition.Scientific reports · 2021Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSepsis and septic shock kill over 270,000 patients per year in the United States. Sepsis transitions from a hyper-inflammatory to a hypo-inflammatory phase. Alcohol dependence is a risk factor for mortality from sepsis. Ethanol (EtOH) exposure impairs pathogen clearance through mechanisms that are not fully understood. Sirtuin 2 (SIRT2) interferes with pathogen clearance in immune cells but its role in the effects of EtOH on sepsis is unknown. We studied the effect of EtOH exposure on hyper- and hypo-inflammation and the role of SIRT2 in mice.
methodsWe exposed C57Bl/6 (WT) mice to EtOH via drinking water and used intraperitoneal cecal slurry (CS)-induced sepsis to study: (i) 7-day survival, (ii) leukocyte adhesion (LA) in the mesenteric microcirculation during hyper- and hypo-inflammation, (iii) peritoneal cavity bacterial clearance, and (iv) SIRT2 expression in peritoneal macrophages. Using EtOH-exposed and lipopolysaccharide (LPS)-stimulated RAW 264.7 (RAW) cell macrophages for 4 hours or 24 hours, we studied: (i) tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and SIRT2 expression, and (ii) the effect of the SIRT2 inhibitor AK-7 on inflammatory response at 24 hours. Lastly, we studied the effect of EtOH on sepsis in whole body Sirt2 knockout (SIRT2KO) mice during hyper- and hypo-inflammation, bacterial clearance, and 7-day survival.
resultsWT EtOH-sepsis mice showed: (i) Decreased survival, (ii) Muted LA in the microcirculation, (iii) Lower plasma TNF-α and IL-6 expression, (iv) Decreased bacterial clearance, and (v) Increased SIRT2 expression in peritoneal macrophages versus vehicle-sepsis. EtOH-exposed LPS-stimulated RAW cells showed: (i) Muted TNF-α, IL-6, and increased IL-10 expression at 4 hours, (ii) endotoxin tolerance at 24 hours, and (iii) reversal of endotoxin tolerance with the SIRT2 inhibitor AK-7. EtOH-exposed SIRT2KO-sepsis mice showed greater 7-day survival, LA, and bacterial clearance than WT EtOH-sepsis mice.
conclusionEtOH exposure decreases survival and reduces the inflammatory response to sepsis via increased SIRT2 expression. SIRT2 is a potential therapeutic target in EtOH with sepsis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.