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NF-κB suppression→cytokine reduction→endothelial protection
Statins' anti-inflammatory and immunomodulatory properties may attenuate the systemic inflammatory response in sepsis by reducing NF-κB activation, cytokine production, and improving endothelial integrity. Evidence includes Mendelian randomization studies and observational analyses showing reduced sepsis incidence in statin users. Large RCTs (e.g., HARP-2) have yielded mixed results, limiting clinical translation.
“Compared with the patients not using statins, those using different classes of statins exhibited a more significant reduction in sepsis, with aHRs (95% CIs) of sepsis being 0.09 (0.05, 0.14), 0.32 (0.31, 0.34), 0.34 (0.32, 0.36), 0.35 (0.32, 0.37), 0.37 (0.34, 0.39), 0.42 (0.38, 0.44), and 0.54 (0.5”
— Optimal statin use for prevention of sepsis in type 2 diabetes mellitus. (2023)DOI“Statins, known for their lipid-lowering effects, also exhibit anti-inflammatory and immunomodulatory properties, suggesting potential benefits in sepsis and AKI.”
— Association between pre-ICU statin use and acute kidney injury and in hospital mortality in obese patients with sepsis. (2025)DOI“Effect of statins on sepsis and inflammatory factors: A Mendelian randomization study.”
— Effect of statins on sepsis and inflammatory factors: A Mendelian randomization study. (2024)DOI“Previous work demonstrated that statins increased survival and inhibited myeloid cell trafficking in a murine model of sepsis, but the exact mechanisms underlying this phenomenon were unclear.”
— Mononuclear phagocyte morphologic response to chemoattractants is dependent on geranylgeranyl pyrophosphate. (2024)DOI“Statins may reduce liver inflammation and prevent injury in sepsis, but their clinical application is limited.”
— Sepsis-associated liver injury: Mechanisms and potential therapeutic targets. (2024)DOI“Statins [Hydroxymethylglutaryl-CoA reductase inhibitors] not only lower cholesterol levels but also have been proposed as adjunctive therapy in sepsis due to their pleiotropic effects.”
— Future of Statins in Sepsis: A Review on Its Safety and Efficacy (2020)DOI“The findings of further analyses, including stratification based on statin usage, dosage, and propensity score matching, consistently reinforced the hypothesis that administering statins to patients with sepsis effectively mitigates their potential APE risk.”
— Association between statin use and acute pulmonary embolism in intensive care unit patients with sepsis: a retrospective cohort study. (2024)DOI“Statin use is associated with improved outcomes following sepsis-related ICU admission, most likely from its pleiotropic properties, characterized by lower 90-day and in-hospital mortality among statin users.”
— The impact of statin use on sepsis mortality. (2024)DOI“Statins were associated with decreased mortality in critically ill patients with sepsis.”
— Statin use during intensive care unit stay is associated with improved clinical outcomes in critically ill patients with sepsis: a cohort study. (2025)DOI“Although observational studies have reported improved outcomes in patients with community-acquired pneumonia or sepsis receiving statins, most RCTs on inpatient statin treatment in sepsis or ventilator-associated pneumonia failed to demonstrate a beneficial effect.”
— Statin therapy in COVID-19 infection. (2020)DOI“The use of statins could decrease the risk of mortality in patients with sepsis during the hospital period.”
— Association between statin administration and outcome in patients with sepsis: A retrospective study. (2025)DOI“In comparison with the non-statin group, the use of different types of statin were associated with reduced 28-day mortality in sepsis patients with AKI.”
— The impact of early use of statin in sepsis patients with acute kidney injury: a study based on MIMIC-IV. (2025)DOI“Given the pharmacological effects of statins in both sepsis and cardiovascular disease, this study aimed to investigate the association between statins use and the prognosis of SIMI.”
— Association between statins use and mortality in critically ill patients with sepsis included myocardial injury: a retrospective cohort study. (2025)DOI“Several studies have demonstrated that statins may reduce the mortality and severity of infectious diseases, such as pneumonia or sepsis.”
— Atorvastatin Reduces the Severity of COVID-19: A Nationwide, Total Population-Based, Case-Control Study (2022)DOI“Therapeutic Effect of Statins and LPS Antibody on Proinflammatory Mediator and Biochemical Markers of Sepsis Rat Model Induced by E. coli”
— Therapeutic Effect of Statins and LPS Antibody on Proinflammatory Mediator and Biochemical Markers of Sepsis Rat Model Induced by E. coli (2020)DOI“Available human studies have shown beneficial effects of statins and PCSK9 inhibitors on pneumonia and sepsis.”
— Statins and PCSK9 inhibitors: What is their role in coronavirus disease 2019? (2020)DOI“Our objective was to assess whether newly diagnosed cancer patients on statins had decreased incidence and mortality of sepsis.”
— Effects of Statins on the Incidence and Mortality of Sepsis in Patients with New Cancer Diagnosis. (2021)DOI“Role of aspirin, beta-blocker, statins, and heparin therapy in septic patients under mechanical ventilation: a narrative review.”
— Role of aspirin, beta-blocker, statins, and heparin therapy in septic patients under mechanical ventilation: a narrative review. (2023)DOI