(1637) Temporal Changes in Immunoparalysis Biomarkers in the Acute Phase of Critical Illness

Introduction: Sepsis is characterized by immunologic heterogeneity, yet rapidly processed clinical biomarkers of hyper- and hypo-inflammation are lacking. This makes it challenging to ascertain a patient's immunologic status real time, thereby hindering clinical decision-making in highly complex patients. Monocyte expression of Human Leukocyte Antigen (mHLA-DR) offers insight into the innate immune system, while absolute lymphocyte count (ALC) provides insight into the adaptive immune system. We hypothesize, ex vivo-stimulated cytokine production, following exposure of whole blood to innate and adaptive immune stimulants, may provide rapid and complementary data that correlate with mHLA-DR and ALC and that may be implemented in a clinical setting.

Methods: Whole blood from 64 critically ill patients (31 sepsis and 33 critically ill non-septic (CINS) controls) was stimulated ex vivo with lipopolysaccharide (LPS), anti-CD3/anti-CD28 antibodies, or phorbol 12-myristate 13-acetate (PMA) for 18 hours. Additionally, ALC was determined by automated cell counting, and mHLA-DR was quantified by flow cytometry. These immunologic assays were performed on the day of critical illness onset, as well as on days 7 and 14 of hospitalization. Concentrations of interferon (IFN-γ), tumor necrosis factor (TNF), and interleukin (IL-6) from ex vivo-stimulated blood were then compared with ALC and mHLA-DR.

Results: All biomarkers of immune function significantly increased over the 14-day recovery window. When comparing sepsis and CINS subgroups with immune responses in the combined cohort, we noted that temporal increases in mHLA-DR were primarily driven by the CINS subset of patients, while the septic subset drove increases in ALC, LPS-induced TNF and IL-6 concentrations (whether normalized to monocyte count or not), and PMA-induced IFN-γ concentrations in the overall cohort. While immunoparalysis biomarkers were not associated with 30-day mortality, stimulated IL-6 production was associated with 30-day hospital readmission in the septic subset.

Conclusions: All immunoparalysis biomarkers indicate steady recovery in immune function over the first two weeks following critical illness onset. However, they also suggest that immunologic phenotyping is needed not only in patients with sepsis but in all critically ill patients.