Enteral and Parenteral Feeding and Monocyte Gene Expression in Critically Ill Patients

Muscle wasting negatively affects morbidity and mortality in critically ill patients. This progressive wasting is accompanied by, in general, a normal muscle PS (protein synthesis) rate. In the present study, we investigated whether muscle protein degradation is increased in critically ill patients with sepsis and which proteolytic enzyme systems are involved in this degradation. Eight patients and seven healthy volunteers were studied. In vivo muscle protein kinetics was measured using arteriovenous balance techniques with stable isotope tracers. The activities of the major proteolytic enzyme systems were analysed in combination with mRNA expression of genes related to these proteolytic systems. Results show that critically ill patients with sepsis have a variable but normal muscle PS rate, whereas protein degradation rates are dramatically increased (up to 160%). Of the major proteolytic enzyme systems both the proteasome and the lysosomal systems had higher activities in the patients, whereas calpain and caspase activities were not changed. Gene expression of several genes related to the proteasome system was increased in the patients. mRNA levels of the two main lysosomal enzymes (cathepsin B and L) were not changed but, conversely, genes related to calpain and caspase had a higher expression in the muscles of the patients. In conclusion, the dramatic muscle wasting seen in critically ill patients with sepsis is due to increased protein degradation. This is facilitated by increased activities of both the proteasome and lysosomal proteolytic systems.

Download Full-text

Association between disease-related malnutrition and innate immunity gene expression in critically ill patients at intensive care unit admission

Central European Journal of Immunology ◽

10.5114/ceji.2020.103393 ◽

2020 ◽

Vol 45 (4) ◽

pp. 414-424

Author(s):

Robert Słotwiński ◽

Aleksandra Dąbrowska ◽

Katarzyna Kosałka ◽

Andrzej Kański ◽

Sylwia Małgorzata Słotwińska

Keyword(s):

Gene Expression ◽

Intensive Care Unit ◽

Innate Immunity ◽

Intensive Care ◽

Intensive Care Unit Admission ◽

Critically Ill ◽

Critically Ill Patients ◽

Immunity Gene ◽

Innate Immunity Gene

Download Full-text

COVID-19 ARDS is characterized by a dysregulated host response that differs from cytokine storm and may be modified by dexamethasone

10.1101/2020.12.28.20248552 ◽

2021 ◽

Author(s):

Aartik Sarma ◽

Stephanie A. Christenson ◽

Eran Mick ◽

Catherine DeVoe ◽

Thomas Deiss ◽

...

Keyword(s):

Gene Expression ◽

Respiratory Tract ◽

Critically Ill ◽

Critically Ill Patients ◽

Host Response ◽

Lower Respiratory Tract ◽

Transcriptional Profiling ◽

Cytokine Storm

AbstractWe performed comparative lower respiratory tract transcriptional profiling of 52 critically ill patients with ARDS from COVID-19 or other etiologies, or without ARDS. We found no evidence of cytokine storm but instead observed complex host response dysregulation driven by genes with non-canonical roles in inflammation and immunity that were predicted to be modulated by dexamethasone. Compared to other viral ARDS, COVID-19 was characterized by impaired interferon-stimulated gene expression.

Download Full-text

Expression of thyroid hormone transporters during critical illness

Acta Endocrinologica ◽

10.1530/eje-09-0290 ◽

2009 ◽

Vol 161 (2) ◽

pp. 243-250 ◽

Cited By ~ 55

Author(s):

Liese Mebis ◽

Deborah Paletta ◽

Yves Debaveye ◽

Björn Ellger ◽

Lies Langouche ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Critical Illness ◽

Thyroid Hormone ◽

Critically Ill ◽

Critically Ill Patients ◽

Rabbit Model ◽

Monocarboxylate Transporter ◽

Expression Levels ◽

Gene Expression Levels

ObjectiveProlonged critically ill patients have low circulating thyroid hormone (TH) levels without a rise in TSH, a condition labeled ‘the low tri-iodothyronine (T3) syndrome’. Currently, it is not clear whether this represents an adaptive response. We examined the role of TH transporters monocarboxylate transporter 8 (MCT8, also known as SLC16A2) and MCT10 in the pathogenesis of the low T3 syndrome in prolonged critical illness.MethodsA clinical observational study in critically ill patients and an intervention study in an in vivo animal model of critical illness. Gene expression levels of MCT8 and MCT10 were measured by real-time PCR.ResultsIn prolonged critically ill patients, we measured increased MCT8 but not MCT10 gene expression levels in liver and skeletal muscle as compared with patients undergoing acute surgical stress. In a rabbit model of prolonged critical illness, gene expression levels of MCT8 in liver and of MCT10 in skeletal muscle were increased as compared with healthy controls. Treatment of prolonged critically ill rabbits with TH (thyroxine+T3) resulted in a downregulation of gene expression levels of MCT8 in liver and of MCT10 in muscle. Transporter expression levels correlated inversely with circulating TH parameters.ConclusionsThese data suggest that alterations in the expression of TH transporters do not play a major role in the pathogenesis of the ‘low T3 syndrome’ but rather reflect a compensatory effort in response to hypothyroidism.

Download Full-text

Profile of the SeptiCyte™ LAB gene expression assay to diagnose infection in critically ill patients

Expert Review of Molecular Diagnostics ◽

10.1080/14737159.2019.1567333 ◽

2019 ◽

Vol 19 (2) ◽

pp. 95-108 ◽

Cited By ~ 6

Author(s):

D. M. Verboom ◽

M. E. Koster-Brouwer ◽

M. R. J. Varkila ◽

M. J. M. Bonten ◽

O. L. Cremer

Keyword(s):

Gene Expression ◽

Critically Ill ◽

Critically Ill Patients ◽

Gene Expression Assay

Download Full-text

Differential Gene Expression in Circulating CD14+ Monocytes Indicates the Prognosis of Critically Ill Patients with Sepsis

Journal of Clinical Medicine ◽

10.3390/jcm9010127 ◽

2020 ◽

Vol 9 (1) ◽

pp. 127 ◽

Cited By ~ 2

Author(s):

Anke Liepelt ◽

Philipp Hohlstein ◽

Hendrik Gussen ◽

Jia Xue ◽

Anna C. Aschenbrenner ◽

...

Keyword(s):

Gene Expression ◽

Disease Severity ◽

Critically Ill ◽

Critically Ill Patients ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Nucleotide Exchange ◽

Activation Pattern ◽

Characteristic Functional ◽

Icu Patients

Critical illness and sepsis are characterized by drastic changes in the systemic innate immune response, particularly involving monocytes. The exact monocyte activation profile during sepsis, however, has remained obscure. Therefore, we prospectively analyzed the gene expression profile of circulating CD14+ monocytes from healthy volunteers (n = 54) and intensive care unit (ICU) patients (n = 76), of which n = 36 had sepsis. RNA sequencing of selected samples revealed that monocytes from septic ICU patients display a peculiar activation pattern, which resembles characteristic functional stages of monocyte-derived macrophages and is distinct from controls or non-sepsis ICU patients. Focusing on 55 highly variable genes selected for further investigation, arachidonate 5-lipoxygenase-activating protein (ALOX5AP) was highly upregulated in monocytes of ICU patients and only normalized during 7 days in the ICU in non-sepsis patients. Strikingly, low monocytic guanine nucleotide exchange factor 10-like protein (ARHGEF10L) mRNA expression was associated with the disease severity and mortality of ICU patients. Collectively, our comprehensive analysis of circulating monocytes in critically ill patients revealed a distinct activation pattern, particularly in ICU patients with sepsis. The association with disease severity, the longitudinal recovery or lack thereof during the ICU stay, and the association with prognosis indicate the clinical relevance of monocytic gene expression profiles during sepsis.

Download Full-text