Innate immunity gene expression changes in critically ill patients with sepsis and disease-related malnutrition

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.

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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.

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The Influence of Innate Immunity Gene Receptors Polymorphisms in Renal Transplant Infections

Transplantation Journal ◽

10.1097/01.tp.0000264999.71318.2b ◽

2007 ◽

Vol 83 (11) ◽

pp. 1493-1500 ◽

Cited By ~ 67

Author(s):

Carlos Cervera ◽

Francisco Lozano ◽

Nuria Saval ◽

Idoia Gimferrer ◽

Ana Iba??ez ◽

...

Keyword(s):

Innate Immunity ◽

Renal Transplant ◽

Immunity Gene ◽

Innate Immunity Gene

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

Diet and Nutrition in Critical Care ◽

10.1007/978-1-4614-7836-2_115 ◽

2015 ◽

pp. 153-162

Author(s):

Dena Arumugam ◽

Stephen C. Gale ◽

Steve E. Calvano

Keyword(s):

Gene Expression ◽

Critically Ill ◽

Critically Ill Patients ◽

Parenteral Feeding

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Innate immunity gene polymorphisms and the risk of colorectal neoplasia

Carcinogenesis ◽

10.1093/carcin/bgt228 ◽

2013 ◽

Vol 34 (11) ◽

pp. 2512-2520 ◽

Cited By ~ 3

Author(s):

C. M. Chang ◽

V. M. Chia ◽

M. J. Gunter ◽

K. A. Zanetti ◽

B. M. Ryan ◽

...

Keyword(s):

Innate Immunity ◽

Gene Polymorphisms ◽

Colorectal Neoplasia ◽

Immunity Gene ◽

Innate Immunity Gene

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Effect of Intravenous 25OHD Supplementation on Bone Turnover and Inflammation in Prolonged Critically Ill Patients

Hormone and Metabolic Research ◽

10.1055/a-1114-6072 ◽

2020 ◽

Vol 52 (03) ◽

pp. 168-178

Author(s):

Catherine Ingels ◽

Ilse Vanhorebeek ◽

Sophie Van Cromphaut ◽

Pieter J. Wouters ◽

Inge Derese ◽

...

Keyword(s):

Vitamin D ◽

Innate Immunity ◽

Critical Illness ◽

Bone Metabolism ◽

Critically Ill ◽

Critically Ill Patients ◽

Healthy Subjects ◽

Mineral Metabolism ◽

Controlled Study ◽

Serum 25Ohd

AbstractCritically ill patients have low circulating 25-hydroxyvitamin D (25OHD), vitamin D binding protein (DBP), and 1,25-dihydroxyvitamin D [1,25(OH)2D]. Low 25OHD is associated with poor outcomes, possibly explained by its effect on bone and immunity. In this prospective, randomized double-blind, placebo-controlled study, we investigated the feasibility of normalizing 25OHD in prolonged (>10 days) critically ill patients and the effects thereof on 1,25(OH)2D, bone metabolism, and innate immunity. Twenty-four patients were included and compared with 24 matched healthy subjects. Patients were randomized to either intravenous bolus of 200 μg 25OHD followed by daily infusion of 15 μg 25OHD for 10 days, or to placebo. Parameters of vitamin D, bone and mineral metabolism, and innate immune function were measured. As safety endpoints, ICU length of stay and mortality were registered. Infusion of 25OHD resulted in a sustained increase of serum 25OHD (from median baseline 9.2 –16.1 ng/ml at day 10), which, however, remained below normal levels. There was no increase in serum 1,25(OH)2D but a slight increase in serum 24,25(OH)2D. Mineral homeostasis, innate immunity and clinical safety endpoints were unaffected. Thus, intravenous 25OHD administration during critical illness increased serum 25OHD concentrations, though less than expected from data in healthy subjects, which suggests illness-induced alterations in 25OHD metabolism and/or increased 25OHD distribution volume. The increased serum 25OHD concentrations were not followed by a rise in 1,25(OH)2D nor were bone metabolism or innate immunity affected, which suggests that low 25OHD and 1,25OHD levels are part of the adaptive response to critical illness.

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