Hyporesponsiveness of natural killer cells and impaired inflammatory responses in critically ill patients

Background: To investigate natural killer (NK) cell activity, circulating cytokine level and peripheral blood mononuclear cell (PBMC) cytokine production status in critically ill patients. Methods: Blood samples were collected <24h after admission from 24 intensive care unit (ICU) patients and 24 age-, sex-, and body mass index (BMI)-matched healthy controls. Serum cytokine concentrations and cytokine production by PBMCs and lipopolysaccharide (LPS)-stimulated PBMCs were measured. Results: The ICU group showed lower NK cell activity than the controls under all conditions and an absence of interferon (IFN)-γ. After adjusting for triglycerides, LDL- and HDL-cholesterol, and glucose, the ICU group exhibited lower serum levels of albumin and interleukin (IL)-12 and higher leukocyte counts and hs-CRP and IL-6 levels than the controls. Non-stimulated PBMCs from ICU patients secreted significantly greater amounts of IL-6 and IL-1β than the controls; however, the production of IL-6, TNF-α and IL-1β in response to LPS stimulation was significantly lower in the ICU group. Conclusions: Significant reductions in NK cell activity and serum IL-12 level, an absence of serum IFN-γ, and decreased cytokine production from LPS-stimulated PBMCs indicate the hyporesponsiveness of NK cells and an impaired early phase inflammatory response in critically ill patients (ClinicalTrials.gov NCT02565589 :). Retrospectively registered; October 1, 2015.