Cytokine response in severe sepsis: predicting and modelling the course of illness

Introduction

Severe sepsis remains one of the most threatening conditions in intensive care. During the progression of sepsis from early hit to multiorgan failure proinflammatory and anti-inflammatory cytokines are released. Cytokines can be used as biomarkers to determine the specific patterns of sepsis progression and association with mortality [1]. These biomarkers were successfully used as predictors in animal studies [2]. Data from humans, especially comparison between children and adults, are limited. Hence, in this study we widely describe systemic cytokine response in this type of patient population.

Methods

Prospective study of 37 subjects (20 children, 17 adults) hospitalized with severe sepsis in intensive care. We measured CRP, procalcitonin, TNF, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-12, TREM-1. ANOVA models were specified using Proc Mixed. Study was fully approved by an ethics committee.

Results

We identified a correlation of CRP levels with mortality or presence of shock (Figure 1). We found a distinct feature of CRP in adults with pronounced dynamic dichotomy in these subjects. Levels of IL-6 were significantly different in adult patients in the context of shock states. High IL-6 levels in the beginning of sepsis were associated with shock during progression of illness. Highest risk of death was in adult patients associated with TREM-1 sustained high after 48 hours after sepsis onset (Figure 2). Otherwise, there was no correlation with death, shock states and SOFA score for PCT, TNF, IL-1β, IL-4, IL-8, IL-10, and IL-12.

Figure 1

SOFA adults. Solid line, SOFA 0 to 12; dashed line, SOFA 13 to 24.

Figure 2

Adults. Solid line, exitus; dashed line, survived.

Conclusions

Response of circulating factors in patients with severe sepsis is heterogeneous in the adult and children population and has some distinct features according to the dynamics of CRP, IL-6 and TREM-1.