Role and Mechanisms of Lipid and Lipoprotein Dysregulation in Sepsis

Role and Mechanisms of Lipid and Lipoprotein Dysregulation in Sepsis

Lipids and lipoproteins (cholesterol and lipid metabolites) are present in sepsis and are highly biologically active regulators of inflammation, but currently the changes in lipid and lipoprotein homeostasis during sepsis are not well understood. This project will investigate the changes in lipid and lipoprotein function, oxidation, metabolites, and changes in gene expression to further our understanding of dysregulated lipid and lipoprotein metabolism in sepsis. We will analyze a bank of samples and make associations with important clinical outcomes (early death, chronic critical illness and sepsis recidivism) as supported by our published work, and will confirm our findings in a small prospective cohort of sepsis patients.

This study will use biobanked samples from a diverse cohort of 165 sepsis patients (UF Jacksonville and UF Gainesville) and will confirm findings in a small prospective cohort of 50 patients. The following will be tested in patient samples:

Aim 1: Test and compare HDL and LDL function (oxidation/transport) in sepsis patients by clinical outcomes of rapid recovery, early death, CCI, and sepsis recidivism.

Aim 2: Determine the changes in lipid homeostasis and patterns of inflammation that occur in sepsis patients by outcome.

Aim 3: Characterize cholesterol & lipoprotein-specific metabolic gene expression in whole blood leukocytes and peripheral blood mononuclear cells from sepsis patients.

Inclusion criteria:

• Patients meeting the Sepsis-3 definition of sepsis or septic shock
• Treatment with an institutional, evidence-based guideline management bundle for sepsis within 24 hrs of sepsis recognition
• Sequential organ failure assessment (SOFA) score will be used for organ failure assessment.

Exclusion criteria:

• a) alternative/confounding diagnosis causing shock (e.g., myocardial infarction or pulmonary embolus)
• b) uncontrollable source of sepsis (e.g., irreversible disease state such as unresectable dead bowel)
• c) advanced directives limiting resuscitative efforts
• d) organ transplant recipient on immunosuppressive agents
• e) known pregnancy
• f) inability to obtain informed consent
• g) HIV/AIDS with CD4 count < 200, h) absolute neutrophil count < 500. These criteria are justified by numerous prior studies.