T-cell receptor activation-associated cytokine release is impaired in septic patients with faecal peritonitis

Introduction

Sepsis is associated with immune hyporesponsiveness but the immunological processes behind this are ill defined.

Methods

This study quantified differences in plasma concentrations of cytokines between septic patients with faecal peritonitis, age and gender-matched surgical patients (without sepsis) and age and gender-matched healthy participants. In addition, cytokine levels were measured in supernatant from peripheralblood mononuclear cells stimulated with anti-CD3 and anti-CD3+anti-CD28, incubated for 4 days. Cytokine concentrations of IL-1β, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17A, IFNγ and TNFα were determined by multiplex cytometric bead array.

Results

Plasma levels of IFNγ and IL-13 were lower in septic patients compared with healthy participants. In contrast, plasma levels of IL-6 (see Figure 1) and IL-8 were increased in septic patients compared with both surgical patients and healthy participants. Plasma levels of IL-10 were significantly higher only in comparison with surgical patients. Following incubation with anti-CD3 and anti-CD3+anti-CD28, concentrations of IL-1β, IL-5, IL-6 (see Figure 1), IL-13, IL-17A, IFNγ and TNFα were markedly decreased in samples from septic patients. In addition, stimulation with anti-CD3+anti-CD28 resulted in lower production of IL-10 in septic patients. Lower concentrations of IL-8 were detected in septic patient samples stimulated with only anti-CD3. We found cytokine levels of IL-12p70 remained unaffected across all groups and stimuli.

Figure 1

Concentration of IL-6 in plasma on day 0 (a) and supernatant on day 4 (b).

Conclusion

We demonstrated a proinflammatory cytokine profile in blood from septic patients, preceding a pan downregulation of all assessed cytokines following in vitro T-cell stimulation. To our knowledge, this study is the first to perform an immune functional assay across these three groups.