The role of obesity in the immune response during sepsis

Abstract

BACKGROUND/OBJECTIVES: Sepsis is one of the most important causes of mortality in the developed world, where almost two-thirds of the population suffer from obesity. Therefore, the coexistence of both conditions has become frequent in clinical practice and a growing number of clinical studies attempts to examine the potential effect of obesity on sepsis with controversial results up to now. The present study investigates how obesity influences the immune response of septic patients, by assessing the number and activation state of adipose tissue macrophages, serum and adipose tissue tumor necrosis factor-alpha (TNF alpha) levels and plasma oxidative stress markers. SUBJECTS/METHODS: The study included 106 patients, divided into four groups (control n = 26, obesity n = 27, sepsis n = 27 and sepsis and obesity n = 26). The number of macrophages in subcutaneous and visceral adipose tissue (SAT and VAT) and their subtypes (M1 and M2) were defined with immunohistochemical staining techniques under light microscopy. TNF alpha mRNA levels were determined in SAT and VAT using real-time reverse transcription-PCR. Serum levels of TNF alpha were determined with sandwich enzyme-linked immunosorbent assay. Plasma oxidative stress was evaluated using selective biomarkers (thiobarbituric acid-reactive substances (TBARS), protein carbonyls and total antioxidant capacity (TAC)). RESULTS: Sepsis increased the total number of macrophages and their M2 subtype in (VAT), whereas obesity did not seem to affect the concentration of macrophages in fat. Obesity increased TNF alpha mRNA levels (P < 0.05) in VAT as well as the plasma TBARS (P < 0.001) and protein carbonyls (P < 0.001) in septic patients. The plasma TAC levels were decreased and the serum TNFa levels were increased in sepsis although they were not influenced by obesity. CONCLUSIONS: Obesity is associated with elevated TNF alpha adipose tissue production and increased oxidative stress biomarkers, promoting the proinflammatory response in septic patients.