| Abstract |
Background: Cell stress induced by severe sepsis (SS) or systemic inflammatory response syndrome (SIRS) presents with acute inflammatory, hormonal, immune and metabolic derangements. Their relation with mitochondrial dysfunction has not been adequately studied.
Objectives: The purpose of the study was to evaluate the longitudinal changes of inflammatory-hormonal response, innate-immunity, bioenergetics and metabolism in critically ill patients, adults and children with severe sepsis and to compare them with patients groups with SIRS and healthy groups (H), adults and children.
Materials / Methods: We studied 68 children (SS / 18, SIRS / 23, H / 27) and 79 adults (SS / 23, SIRS / 23, H / 33) on 1, 3 and 5 day of hospitalization. Body Mass Index (BMI) z-scores and disease severity scores (PeLOD, APACHE, TISS, SOFA) were calculated. Cardiac contractility (EF, SF), troponin (Tn) and lactate were measured, as well as energy consumption (EE) with Gas Module E-COVX, ATP in white blood cells with luciferase luminescent assay, glutamine and NO2 / NO3 levels with high-pressure liquid chromatography (HPLC), lipid peroxidation products (TBARS) by colorimetric assay, resistin, serum antiponectin and extracellular Heat Shock Proteins (HSP) HSP90α, serum HSP72, adiponectin and resistin by ELISA.Intracellular Heat Shock Proteins (HSP72, HSP90α) expressions by flow cytometry.
Results: Longitudinal both in adults (ICU) and children (PICU), resistin, dexponcepin, extracellular HPS72 and 90a values showed a sustained pattern of stimulation throughout the acute 5-day phase. In this period, VO2, VCO2, EE showed a hypometabolic pattern similar in children and adults.The increased expression of NO3, NO2, TBARS and adiponectin in sepsis showed a diffuse pattern relating to their age-related expression per age group. Mitochondrial bioenergy was longitudinal reduced in adults and children who did not survive compared to survivors, and was accompanied by significantly reduced metabolism and hypometabolic patterns on days 3 and 5 (p <0.05). Surviving patients had a significant variation in baseline BVR, lactate, EU, VO2, VCO2 and metabolic profile compared to patients who died, who showed inability to recover hypometabolism or antioxidant status on day 5.
Conclusion: SS is characterized from longitudinally stronger intracellular repression of ATP, HPS72, HSP90α, metabolism (EE, albumin, glutamine) and extracellular induction of inflammatory hormones (resistin) and innate immunity proteins signaling acute stress danger (HSP72) compared to SIRS. 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, hypometabolism, and persistently increased resistin and adiponectin are associated with poor outcome.
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