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

Abstract

The aim of this study was an attempt to determine whether the expression of genes involved in innate antibacterial response (TL R2, NOD 1, TRAF6, HMGB 1 and Hsp70) in peripheral blood leukocytes in critically ill patients, may undergo significant changes depending on the severity of the infection and the degree of malnutrition. The study was performed in a group of 128 patients with infections treated in the intensive care and surgical ward. In 103/80.5% of patients, infections had a severe course (sepsis, severe sepsis, septic shock, mechanical ventilation of the lungs). Clinical monitoring included diagnosis of severe infection (according to the criteria of the ACC P/SCC M), assessment of severity of the patient condition and risk of death (APACHE II and SAPS II), nutritional assessment (NRS 2002 and SGA scales) and the observation of the early results of treatment. Gene expression at the mRNA level was analyzed by real-time PCR. The results of the present study indicate that in critically ill patients treated in the IC U there are significant disturbances in the expression of genes associated with innate antimicrobial immunity, which may have a significant impact on the clinical outcome. The expression of these genes varies depending on the severity of the patient condition, severity of infection and nutritional status. Expression disorders of genes belonging to innate antimicrobial immunity should be diagnosed as early as possible, monitored during the treatment and taken into account during early therapeutic treatment (including early nutrition to support the functions of immune cells).

The soluble tumor necrosis factor receptor 1 as a potential early diagnostic and prognostic markers in intensive care unit patients with severe infections

“…It is also confirmed by our earlier study in a homogeneous group of patients with and without infections, who were operated due to colorectal cancer [51]. On the other hand, it was shown that in septic patients treated in an ICU during the first stage of response to an injury and infection, in leucocytes, an increasing expression of genes that code the proteins of early immune response could be a diagnostic marker [7,[52][53][54]. However, genetic tests are still poorly available.…”

Reference Genes for Quantitative qPCR Analyses in Monocytes of Septic Patients

“…The use of GAPDH to normalize gene expression was reported in mononuclear cells from septic patients [16] and in an experimental septic model using immortalized monocyte [27]. GAPDH was considered herein as the most stable gene by the NormFinder analysis.…”

“…Only six studies reported monocyte/macrophage gene expression results in septic conditions using different experimental approaches mostly in in vitro studies using murine bone marrow-derived macrophages and J774A1 murine macrophage cell line [11][12][13][14][15][16]. The followings were used as reference genes in the mentioned studies: 18S (18S RNA ribosomal), ACTB (beta actin), B2M (beta 2-microglobulin), GAPDH (glyceraldehyde 3-phosphate dehydrogenase), GUSB (glucuronidase beta), HMBS (hydroxymethylbilane synthase), HNRNPAB (heterogeneous nuclear ribonucleoprotein A/B), HPRT1 (hypoxanthine phosphoribosyltransferase 1), MAU2 (MAU2 chromatid cohesion factor homolog), PGK1 (phosphoglycerate kinase 1), PPIA (peptidylprolyl isomerase A), PPIB (peptidylprolyl cis-trans isomerase B), RPL13A (ribosomal protein L13a), STX5A (syntaxin 5), YWHAZ (14-3-3 protein zeta/delta).…”

Preoperative hypoalbuminemia is associated with an increased risk for intra-abdominal septic complications after primary anastomosis for Crohn’s disease

“…Serum albumin is an important material for wound healing and collagen synthesis at the anastomosis site, while hypoproteinemia can give rise to tissue edema and collagen synthesis disorders, resulting in the high risk of an anastomotic leakage [ 34 , 35 ]. The serum albumin also has an effect on immune respond [ 36 , 37 ]. A study by Slotwinski et al .…”

“…A study by Slotwinski et al . demonstrates that critically ill patients treated in the intensive care unit (ICU) had significant disturbances in the expression of genes associated with innate antimicrobial immunity, depending on nutritional status, and may have a significant impact on the clinical outcomes [ 36 ]. A study retrospectively analysed 324 patients with IBD and found that the presence of low serum albumin were shared common risk factors for a low serum IgG or IgM level [ 37 ].…”