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Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit.

ABSTRACT: The use of glutamine as a dietary supplement is associated with a reduced risk of infection. We hypothesized that the underlying mechanism could be an increase in the expression and/or functionality of Toll-like receptors (TLR), key receptors sensing infections. The objective of this study was to evaluate whether glutamine supplementation alters the expression and functionality of TLR2 and TLR4 in circulating monocytes of trauma patients admitted to the intensive care unit (ICU).We designed a prospective, randomized and single-blind study. Twenty-three patients received parenteral nutrition (TPN) with a daily glutamine supplement of 0.35 g/kg. The control group (20 patients) received an isocaloric-isonitrogenated TPN. Blood samples were extracted before treatment, at 6 and 14 days. Expression of TLR2 and TLR4 was determined by flow cytometry. Monocytes were stimulated with TLR specific agonists and cytokines were measured in cell culture supernatants. Phagocytic ability of monocytes was also determined.Basal characteristics were similar in both groups. Monocytes from patients treated with glutamine expressed the same TLR2 levels as controls before treatment (4.9 ± 3.5 rmfi vs. 4.3 ± 1.9 rmfi, respectively; P = 0.9), at Day 6 (3.8 ± 2.3 rmfi vs. 4.0 ± 1.7 rmfi, respectively; P = 0.7) and at Day 14 (4.1 ± 2.1 rfim vs. 4.6 ± 1.9 rmfi, respectively; P = 0.08). TLR4 levels were not significantly different between the groups before treatment: (1.1 ± 1 rmfi vs 0.9 ± 0.1 rmfi respectively; P = 0.9), at Day 6 (1.1 ± 1 rmfi vs. 0.7 ± 0.4 rmfi respectively; P = 0.1) and at Day 14 (1.4 ± 1.9 rmfi vs. 1.0 ± 0.6 rmfi respectively; P = 0.8). No differences in cell responses to TLR agonists were found between groups. TLR functionality studied by phagocytosis did not vary between groups.In trauma patients in the intensive care unit, TPN supplemented with glutamine does not improve the expression or the functionality of TLRs in peripheral blood monocytes.ClinicalTrials.gov Identifier: NCT01250080.

SUBMITTER: Perez-Barcena J

PROVIDER: S-EPMC3219991 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit.

Pérez-Bárcena Jon J Crespí Catalina C Regueiro Verónica V Marsé Pedro P Raurich Joan M JM Ibáñez Jordi J García de Lorenzo-Mateos Abelardo A Bengoechea José A JA

Critical care (London, England) 20101224 6

<h4>Introduction</h4>The use of glutamine as a dietary supplement is associated with a reduced risk of infection. We hypothesized that the underlying mechanism could be an increase in the expression and/or functionality of Toll-like receptors (TLR), key receptors sensing infections. The objective of this study was to evaluate whether glutamine supplementation alters the expression and functionality of TLR2 and TLR4 in circulating monocytes of trauma patients admitted to the intensive care unit ( ...[more]

PMID: 21184675

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Project description:BackgroundAdvancing age is a strong risk factor for adverse outcomes across multiple disease processes. However, septic surgical and trauma patients are unique in that they incur two or more inflammatory insults. The effects of advanced age on sepsis pathophysiology and outcomes remain unclear.MethodsWe performed a single-center, prospective observational cohort study of surgical intensive care unit patients with severe sepsis/septic shock. Peripheral blood was collected for genomic, cytokine, and biomarker analysis at 0.5 day, 1 day, 4 days, 7 days, 14 days, 21 days, and 28 days after sepsis onset. Based on sensitivity analysis, cohorts were defined as "young" (<55 years) and "aged" (≥55 years). We compared age-defined cohorts to determine differences in patient characteristics, biomarker profiles, and clinical outcomes.ResultsThe cohort included 173 patients with severe sepsis (n = 93; 53.8%) or septic shock (n = 80; 46.2%), with a mean age of 60.9 (±14.5) years. Intra-abdominal sepsis was the leading source (n = 81; 46.8%), followed by necrotizing soft tissue infection (n = 33, 19.1%) and pneumonia (n = 30; 17.3%). Aged patients had a higher comorbidity burden, but were otherwise similar to the young cohort. The aged cohort had a higher severity of early physiologic derangement (median APACHE II, 23 vs. 18; p = 0.002), greater incidence of multiple organ failure (64.3% vs. 40.4%, p = 0.006), and hospital mortality (15.9% vs. 2.1%; p = 0.016). Six-month mortality was significantly higher in the aged cohort as compared with young cohort (31% vs. 9%; p = 0.003). Aged septic patients biomarker trajectories suggestive of persistent immunosuppression (absolute lymphocyte count, soluble programed death ligand-1) and catabolism (Urine 3MH-Cr ratio, insulin growth factor, IGF1BP3, albumin) out to 28 days after sepsis.ConclusionAged, critically ill surgical patients have greater organ dysfunction and incidence of adverse clinical outcomes after sepsis. Biomarker profiles suggest an immunophenotype of persistent immunosuppression and catabolism. Advanced age may necessitate novel therapeutic strategies to promote multisystem organ recovery and improve survival after sepsis.Level of evidencePrognostic, level II.

Project description:BackgroundThe protective cardiovascular effect of high-density lipoproteins (HDLs) is considered to chiefly rely on reverse cholesterol transport from peripheral tissues back to the liver. However, HDL particles display pleiotropic properties, including anti-inflammatory, anti-apoptotic or antioxidant functions. Some studies suggest that HDL concentration decreases during sepsis, and an association was reported between low HDL levels and a poor outcome. Like sepsis, trauma is also associated with a systemic inflammatory response syndrome. However, no study has yet explored changes in lipid profiles during trauma. We sought to compare lipid profiles between sepsis and trauma patients in intensive care unit (ICU). In septic patients, we analyzed the association between lipid profile, severity and prognosis.MethodsA prospective, observational, single-centered study was conducted in a surgical ICU. For each patient, total cholesterol, HDL, triglyceride and low-density lipoprotein cholesterol levels were assessed at admission. Short-term prognosis outcome was prospectively assessed.ResultsSeventy-five consecutive patients were admitted (50 sepsis and 25 trauma). There was no difference in SOFA and SAPSII scores between the two groups. Patients with sepsis had lower total cholesterol levels than patients with trauma. Regarding the lipoprotein profile, only HDLs differed significantly between the two groups (median [IQR] = 0.33 mmol/l [0.17-0.78] in sepsis patients versus median [IQR] = 0.99 mmol/l [0.74-1.28] in trauma patients; P < 0.0001). Whereas ICU mortality was not associated with lipid levels in the sepsis group, a significant negative correlation was found between HDL concentration and the length of ICU stay (r = -0.35; P = 0.03) in the group of survivor septic patients at ICU discharge. In addition, poor outcome defined as death or a SOFA score >6 at day 3 was associated with lower HDL levels (median [IQR] = 0.20 mmol/l [0.11-0.41] vs. 0.35 mmol/l [0.19-0.86] in patients with poor outcome versus others; P = 0.03).ConclusionsLipid profile was totally different between sepsis and trauma in ICU patients: HDL levels were low in septic patients, whereas their concentration was not altered in trauma patients. This major difference reinforces the necessity to explore the therapeutic potential of HDL in sepsis.

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Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit.

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Lack of effect of glutamine administration to boost the innate immune system response in trauma patients in the intensive care unit.

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