Immunometabolic chaos in septic shock

• DOI: 10.1093/jleuko/qiae211
• Publication Date: 2024-09-28T12:57:47Z
• Authors: Deepmala Shrestha; Bishnu D Pant; Sanjoy Roychowdhury; Anugraha Gandhirajan; Emily Cross; Mamta Chhabria; Seth R Bauer; Margaret Jeng; Megan Mitchell; Omar Mehkri; Fatima Zaidi; Akash Ahuja; Xiaofeng Wang; Yuxin Wang; Christine McDonald; Michelle S Longworth; Thaddeus S Stappe...; George R Stark; Rachel G Scheraga; Vidula Vachharajani

Abstract Septic shock is associated with over 40% mortality. The immune response in septic tightly regulated by cellular metabolism and transitions from early hyper-inflammation to later hypo-inflammation. Patients are susceptible secondary infections during magnitude of the metabolic dysregulation effect plasma metabolites on circulating cells not reported. We hypothesized that accumulated affect Our study took a unique approach. Using peripheral blood adult patients healthy controls, we studied: 1. Whole stimulation ± E. Coli lipopolysaccharide (LPS: endotoxin) analyze TNF protein, 2. Plasma metabolomic profile Metabolon. Inc. 3. exposed mononuclear (PBMCs) controls commercially available carbohydrate, amino acid, fatty acid studied LPS. report that: whole control group showed significantly upregulated while remained endotoxin tolerant, biomarker for A significant accumulation ceramide, sphingomyelin, TCA cycle pathway plasma. In vitro exposure five repressed two inflammatory PBMCs conclude endotoxin-tolerant phenotype simultaneous multiple pathways, these fundamentally influence cells.