Immune suppression is associated with enhanced systemic inflammatory, endothelial and procoagulant responses in critically ill patients

by Xanthe Brands, Fabrice Uhel, Lonneke A. van Vught, Maryse A. Wiewel, Arie J. Hoogendijk, René Lutter, Marcus J. Schultz, Brendon P. Scicluna, Tom van der Poll

Objective

Patients admitted to the Intensive Care Unit (ICU) oftentimes show immunological signs of immune suppression. Consequently, immune stimulatory agents have been proposed as an adjunctive therapy approach in the ICU. The objective of this study was to determine the relationship between the degree of immune suppression and systemic inflammation in patients shortly after admission to the ICU.Design: An observational study in two ICUs in the Netherlands.

Methods

The capacity of blood leukocytes to produce cytokines upon stimulation with lipopolysaccharide (LPS) was measured in 77 patients on the first morning after ICU admission. Patients were divided in four groups based on quartiles of LPS stimulated tumor necrosis factor (TNF)-α release, reflecting increasing extents of immune suppression. 15 host response biomarkers indicative of aberrations in inflammatory pathways implicated in sepsis pathogenesis were measured in plasma.

Results

A diminished capacity of blood leukocytes to produce TNF-α upon stimulation with LPS was accompanied by a correspondingly reduced ability to release of IL-1β and IL-6. Concurrently measured plasma concentrations of host response biomarkers demonstrated that the degree of reduction in TNF-α release by blood leukocytes was associated with increasing systemic inflammation, stronger endothelial cell activation, loss of endothelial barrier integrity and enhanced procoagulant responses.

Conclusions

In patients admitted to the ICU the strongest immune suppression occurs in those who simultaneously display signs of stronger systemic inflammation. These findings may have relevance for the selection of patients eligible for administration of immune enhancing agents.

Trial registration

ClinicalTrials.gov identifier NCT01905033.