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Lipid Mediators in Critically Ill Patients: A Step Towards Precision Medicine.

ABSTRACT: A dysregulated response to systemic inflammation is a common pathophysiological feature of most conditions encountered in the intensive care unit (ICU). Recent evidence indicates that a dysregulated inflammatory response is involved in the pathogenesis of various ICU-related disorders associated with high mortality, including sepsis, acute respiratory distress syndrome, cerebral and myocardial ischemia, and acute kidney injury. Moreover, persistent or non-resolving inflammation may lead to the syndrome of persistent critical illness, characterized by acquired immunosuppression, catabolism and poor long-term functional outcomes. Despite decades of research, management of many disorders in the ICU is mostly supportive, and current therapeutic strategies often do not take into account the heterogeneity of the patient population, underlying chronic conditions, nor the individual state of the immune response. Fatty acid-derived lipid mediators are recognized as key players in the generation and resolution of inflammation, and their signature provides specific information on patients' inflammatory status and immune response. Lipidomics is increasingly recognized as a powerful tool to assess lipid metabolism and the interaction between metabolic changes and the immune system via profiling lipid mediators in clinical studies. Within the concept of precision medicine, understanding and characterizing the individual immune response may allow for better stratification of critically ill patients as well as identification of diagnostic and prognostic biomarkers. In this review, we provide an overview of the role of fatty acid-derived lipid mediators as endogenous regulators of the inflammatory, anti-inflammatory and pro-resolving response and future directions for use of clinical lipidomics to identify lipid mediators as diagnostic and prognostic markers in critical illness.

SUBMITTER: Cioccari L

PROVIDER: S-EPMC7724037 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Lipid Mediators in Critically Ill Patients: A Step Towards Precision Medicine.

Cioccari Luca L Luethi Nora N Masoodi Mojgan M

Frontiers in immunology 20201125

A dysregulated response to systemic inflammation is a common pathophysiological feature of most conditions encountered in the intensive care unit (ICU). Recent evidence indicates that a dysregulated inflammatory response is involved in the pathogenesis of various ICU-related disorders associated with high mortality, including sepsis, acute respiratory distress syndrome, cerebral and myocardial ischemia, and acute kidney injury. Moreover, persistent or non-resolving inflammation may lead to the s ...[more]

PMID: 33324417

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Project description:Objective: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill ICU patients positive for COVID19 vs. those negative for COVID19 to better understand the COVID19 associated host response. Design: Transcriptome profiling of buffy coat cells via ribonucleic acid sequencing (RNAseq) at the time of admission to the ICU. Setting: Tertiary care ICU and academic laboratory. Subjects: All patients admitted to the ICU suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Interventions: None. Measurement and Main Results: Age- and sex-matched ICU patients that were either COVID19+ (PCR positive, 2 genes) or COVID19- (PCR negative) were enrolled. Cohorts were well-balanced with the exception that COVID19- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19+ patients were more likely to suffer bilateral pneumonia compared to COVID19- patients. Further, the mortality rate for this cohort of COVID19+ ICU patients was 29%. Transcriptional analysis revealed that when compared to COVID19- patients, the altered transcriptional responses of leukocytes in critically ill COVID19+ ICU patients appeared to be associated with multiple interrelated outcomes, including but not limited to robust interferon (IFN)-associated transcriptional responses, a marked decrease in the transcriptional activity of genes contributing to protein synthesis and the dysregulated expression of genes that contribute to coagulation, platelet activation, Toll-like receptor activation, neurotrophin signaling, and protein SUMOylation/ubiquitination. Conclusions: COVID19+ patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19- patients. Identification of this profile provides guidance for future targeted studies exploring novel prognostic/therapeutic aspects of COVID19.

Dataset Information

Lipid Mediators in Critically Ill Patients: A Step Towards Precision Medicine.

Publications

Lipid Mediators in Critically Ill Patients: A Step Towards Precision Medicine.

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