Longitudinal Profiles of Metabolism and Bioenergetics Associated with Innate Immune Hormonal Inflammatory Responses and Amino‐Acid Kinetics in Severe Sepsis and Systemic Inflammatory Response Syndrome in Children

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Experimental data indicate that sepsis influences the mitochondrial function and metabolism. We aim to investigate longitudinal bioenergetic, metabolic, hormonal, amino‐acid, and innate immunity changes in children with sepsis.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Sixty‐eight children (sepsis, 18; systemic inflammatory response syndrome [SIRS], 23; healthy controls, 27) were enrolled. Plasma amino acids were determined by high‐performance liquid chromatography (HPLC); flow‐cytometry expressed as mean fluorescence intensity (MFI) of heat shock protein (HSP) levels from monocytes (m) and neutrophils (n); resistin, adiponectin, and extracellular (e) HSPs evaluated by ELISA; ATP levels in white blood cells by luciferase luminescent assay; lipid peroxidation products (TBARS) by colorimetric test; nitrite and nitrate levels by chemiluminescent assay; biliverdin reductase (BVR) activity by enzymatic assay; and energy‐expenditure (EE) by E‐COVX.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Resistin, eHSP72, eHSP90α, and nitrate were longitudinally higher in sepsis compared with SIRS (<jats:italic>p</jats:italic><0.05); mHSP72, nHSP72, VO<jats:sub>2</jats:sub>, VCO<jats:sub>2</jats:sub>, EE, and metabolic pattern were repressed in sepsis compared with SIRS (<jats:italic>p</jats:italic><0.05). Septic patients had lower ATP and TBARS compared with controls on day 1, lower ATP compared with SIRS on day 3 (<jats:italic>p</jats:italic><0.05), but higher levels of BVR activity. Sepsis exhibited higher phenylalanine levels on day 1, serine on day 3; lower glutamine concentrations on days 3 and 5 (<jats:italic>p</jats:italic><0.05). Resistin, inversely related to ATP, was independently associated with sepsis, along with mHSP72 and eHSP90α (<jats:italic>p</jats:italic><0.05); TBARS and VO<jats:sub>2</jats:sub> were independently associated with organ failure (<jats:italic>p</jats:italic><0.05)). Septic nonsurvivors had malnutrition, persistently repressed metabolism, mHSP72, and induced resistin and adiponectin (<jats:italic>p</jats:italic><0.05).</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>A pattern of early longitudinal induction of metabolic‐hormones and eHSP72/HSP90α, repression of bioenergetics and innate immunity, hypo‐metabolism, and amino‐acid kinetics changes discriminate sepsis from SIRS; malnutrition, hypo‐metabolism, and persistently increased resistin and adiponectin are associated with poor outcome.</jats:p></jats:sec>