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 <24 h 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-1ß than the controls; however, the production of IL-6, TNF-α and IL-1ß 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.

Effect of Immune-Enhancing Enteral Nutrition Enriched with or without Beta-Glucan on Immunomodulation in Critically Ill Patients.

We investigated whether high-protein enteral nutrition with immune-modulating nutrients (IMHP) enriched with ß-glucan stimulates immune function in critically ill patients. In a randomized double-blind placebo-controlled study, 30 patients consumed one of three types of enteral nutrition: a control or IMHP with and without ß-glucan. The IMHP with ß-glucan group showed increases in natural killer (NK) cell activities relative to the baseline, and greater increases were observed in NK cell activities relative to the control group after adjusting for age and gender. The IMHP groups with and without ß-glucan had greater increases in serum prealbumin and decreases in high-sensitivity C-reactive protein (hs-CRP) than the control group. The control group had a greater decrease in peripheral blood mononuclear cell (PBMC) interleukin (IL)-12 production than the IMHP with and without ß-glucan groups. In all patients, the change (Δ) in hs-CRP was correlated with Δ prealbumin and Δ PBMC IL-12, which were correlated with ΔNK cell activity and Δ prealbumin. This study showed beneficial effects of a combination treatment of ß-glucan and IMHP on NK cell activity. Additionally, strong correlations among changes in NK cell activity, PBMC IL-12, and hs-CRP suggested that ß-glucan could be an attractive candidate for stimulating protective immunity without enhanced inflammation (ClinicalTrials.gov: NCT02569203).