The role of obesity in the immune response during sepsis.

A S Kolyva,I G Habeos,S F Assimakopoulos,E E Solomou,G Skroubis,N Goutzourelas,V Zolota,D Kouretas,C A Gogos,D Mpatsoulis

doi:10.1038/nutd.2014.34

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 (TNFα) 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. TNFα mRNA levels were determined in SAT and VAT using real-time reverse transcription-PCR. Serum levels of TNFα 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 TNFα 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 TNFα levels were increased in sepsis although they were not influenced by obesity.Conclusions:Obesity is associated with elevated TNFα adipose tissue production and increased oxidative stress biomarkers, promoting the proinflammatory response in septic patients.

Highlights

Sepsis is defined as the systemic inflammatory response syndrome attributed to infection
Single CD68+, CD206+ or CD80+ cells were dispersed throughout the parenchyma in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), whereas ‘crown’-like arrangements of macrophages around a single adipocyte were occasionally observed (Figure 1)
Numerous clinical studies have attempted to investigate the potential effects of obesity on the outcome of septic patients with controversial results up to now.[18,36,37,38]

Summary

INTRODUCTION

Sepsis is defined as the systemic inflammatory response syndrome attributed to infection. The present study was undertaken to investigate the effect of obesity in the immunologic response in sepsis, by studying the potential alterations in: (a) the adipose tissue macrophages and In this prospective study, a total of 106 patients (51 females and 55 males), who were admitted to Patras University General Hospital in Greece during a 5-year period (October 2008 to May 2013) were enrolled. For the concentration of TBARS, a slightly modified assay of Keles et al.[33] was used According to this method, 100 μl of plasma was mixed with 500 μl of 35% trichloroacetic acid (Merck, Darmstadt, Germany) and 500 μl of Tris–HCl (Sigma-Aldrich, St Louis, MO, USA) (200 mM, pH 7.4) and incubated for 10 min at room temperature.

RESULTS

DISCUSSION

CONFLICT OF INTEREST