Dataset Information

Omega-3 vs. omega-6 lipid emulsions exert differential influence on neutrophils in septic shock patients: impact on plasma fatty acids and lipid mediator generation.

ABSTRACT:

Objective

To compare the effects of a conventional omega-6 lipid infusion and a fish oil based (omega-3) lipid infusion for parenteral nutrition on neutrophil function, lipid mediators, and plasma free fatty acids.

Design and setting

Open-label, randomized, pilot study in a university hospital medical intensive care unit and experimental laboratory.

Patients and participants

Ten patients with septic shock and eight healthy controls.

Interventions

Patients (five per group) requiring parenteral nutrition received intravenously either a omega-3 or a omega-6 lipid emulsion for a 10-day period.

Measurements and results

At baseline levels of plasma free fatty acids were elevated several-fold, including high concentrations of the omega-6 lipid precursor arachidonic acid (AA). Neutrophils isolated from septic patients displayed markedly reduced responsiveness to ex vivo stimulation, including lipid mediator generation [leukotrienes (LT), PAF], respiratory burst, and phosphoinositide hydrolysis signaling. Under the omega-6 lipid infusion regimen abnormalities in plasma free fatty acids and impairment of neutrophil functions persisted or worsened. In contrast, a rapid switch in the plasma free fatty acid fraction to predominance of the omega-3 acids eicosapentaenoic acid and docosahexaenoic acid over AA occurred in response to omega-3 lipid infusion. LTB(5), in addition to LTB(4), appeared upon neutrophil stimulation originating from these patients, and neutrophil function was significantly improved in the omega-3 lipid group.

Conclusions

omega-3 vs. omega-6 lipid emulsions differentially influence the plasma free fatty acid profile with impact on neutrophil functions. Lipid-based parenteral nutrition in septic patients may thus exert profound influence on sequelae and status of immunocompetence and inflammation.

SUBMITTER: Mayer K

PROVIDER: S-EPMC7187949 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:A reanalysis of the ALBIOS trial suggested that patients with septic shock - defined by vasopressor-dependent hypotension in the presence of severe sepsis (Shock-2) - had a survival benefit when treated with albumin. The new septic shock definition (Shock-3) added the criterion of a lactate threshold of 2 mmol/L. We investigated how the populations defined according to Shock-2 and Shock-3 differed and whether the albumin benefit would be confirmed. METHODS:This is a retrospective analysis of the ALBIOS study, a randomized controlled study conducted between 2008 and 2012 in 100 intensive care units in Italy comparing the administration of 20% albumin and crystalloids versus crystalloids alone in patients with severe sepsis or septic shock. We analyzed data from 1741 patients from ALBIOS with serum lactate measurement available at baseline. We compared group size, physiological variables and 90-day mortality between patients defined by Shock-2 and Shock-3 and between the albumin and crystalloid treatment groups. RESULTS:We compared the Shock-2 and the Shock-3 definitions and the albumin and crystalloid treatment groups in terms of group size and physiological, laboratory and outcome variables. The Shock-3 definition reduced the population with shock by 34%. The Shock-3 group had higher lactate (p?<?0.001), greater resuscitation-fluid requirement (p?=?0.014), higher Simplified Acute Physiology Score II (p?<?0.001) and Sepsis-related Organ Failure Assessment scores (p?=?0.022), lower platelet count (p?=?0.002) and higher 90-day mortality (46.7% vs 51.9%; p?=?0.031). Albumin decreased mortality in Shock-2 patients compared to crystalloids (43.5% vs 49.9%; 12.6% relative risk reduction; p?=?0.04). In patients defined by Shock-3 a similar benefit was observed for albumin with a 11.3% relative risk reduction (48.7% vs 54.9%; 11.3% relative risk reduction; p?=?0.22). CONCLUSIONS:The Sepsis-3 definition reduced the size of the population with shock and showed a similar effect size in the benefits of albumin. The Shock-3 criteria will markedly slow patients' recruitment rates, in view of testing albumin in septic shock. TRIAL REGISTRATION:ClinicalTrials.gov, number NCT00707122 . Registered on 30 June 2008.

Project description:IntroductionImpaired T cell function in sepsis is associated with poor outcome, but the mechanisms are unclear. In cancer, arginase-expressing myeloid derived suppressor cells (MDSCs) deplete arginine, impair T cell receptor CD3 zeta-chain expression and T cell function and are linked to poor clinical outcome, but their role during acute human infectious disease and in particular sepsis remains unknown. Hypoarginemia is prevalent in sepsis. This study aimed to determine whether neutrophils that co-purify with PBMC express arginase, and if arginine depletion constrains T cell CD3 zeta-chain expression and function in human sepsis.MethodsUsing flow cytometry, cell culture, HPLC, arginase activity and mRNA detection, our study examined whether neutrophils, with reduced buoyant density isolated in the Ficoll interface, metabolise L-arginine and suppress T cell proliferation in sepsis. A total of 35 sepsis patients (23 with septic shock) and 12 hospital controls in a tertiary referral hospital in tropical Australia were evaluated.ResultsOnly sepsis patients had interphase neutrophils, neutrophils co-purifying with mononuclear cells (?1.077 specific gravity). The percentage of interphase neutrophils in sepsis was proportional to sepsis severity and correlated with plasma IL-6 concentrations. Ex vivo, sepsis-derived interphase neutrophils expressed arginase, metabolised culture L-arginine and suppressed T cell proliferation and CD3 zeta-chain expression. In vivo, in septic shock there was a longitudinal inverse association between interphase neutrophil number and CD3 zeta-chain expression. Depletion or inhibition of interphase neutrophils in vitro restored zeta-chain expression and T cell function.ConclusionsFor the first time during an acute human infection, interphase neutrophils that express arginase were found to circulate in sepsis, in proportion to disease severity. These neutrophil-MDSCs impair T cell CD3 zeta-chain expression and T cell function via L-arginine metabolism, and likely contribute to the T cell dysfunction seen in sepsis. Modulation of neutrophil-MDSC or their downstream effects warrant consideration as targets for novel adjunctive therapies in sepsis.