RESUMEN
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).
RESUMEN
The study was carried out to investigate changes in gene expression of innate antibacterial signaling pathways in patients with pancreatic cancer. Expression of the following genes was measured in peripheral blood leukocytes of 55 patients with pancreatic adenocarcinoma using real-time polymerase chain reaction (RT-PCR): TLR4, NOD1, MyD88, TRAF6 and HMGB1. The levels of expression of TLR4, NOD1 and TRAF6 genes were significantly elevated (p = 0.007; p = 0.001 and p = 0.01, respectively), while MyD88 expression was markedly reduced (p = 0.0002), as compared to controls. Expression of TLR4 and NOD1 exceeded the normal level more than 3.5-fold and there was a significant correlation found between the expression of these genes (r = 0.558, p < 0.001). TLR4, NOD1 and MyD88 genes were expressed at a similar level both before and after surgery. No significant changes in the expression of HMGB1 gene were observed. The results of the study clearly indicate abnormal expression of genes belonging to innate antibacterial signaling pathways in peripheral blood leukocytes of patients with pancreatic cancer, which may lead to leukocyte dysfunction. Overexpression of TLR4, NOD1 and TRAF6 genes, and decreased MyD88 gene expression may contribute to chronic inflammation and tumor progression by up-regulation of the innate antibacterial response. The parameters tested are useful for monitoring innate immunity gene disorders and pancreatic cancer progression.
RESUMEN
OBJECTIVE: To investigate whether early enteral immunonutrition in comparison with standard enteral feeding affects the systemic production of pro- and anti-inflammatory cytokines in malnourished patients after pancreaticoduodenectomy with an uneventful postoperative course. DESIGN: Prospective, randomized study. PARTICIPANTS: Forty-one patients who had undergone pancreaticoduodenectomy. INTERVENTIONS: Patients received early enteral standard nutrition (No. 22) or enteral immunonutrition (No. 19). MAIN OUTCOME MEASURES: Cytokines and cytokine inhibitors (IL-1 beta, TNF-alpha, IL-6, IL-8, IL-10, IL-1ra, and sTNFRI) were determined before and on days 1, 3, 7, 10 and 14 after surgery using the ELISA test. RESULTS: Serum concentrations of IL-1ra in the early post-operative period were significantly higher in patients treated with enteral immunonutrition than in those treated with the standard diet (day 7: P<0.001; day 10: P=0.002; day 14: P=0.005). Similar results were observed for IL-6 (day 10: P=0.017; day 14: P=0.001), IL-8 (day 1: P=0.011; days 3, 7, 10, and 14: P<0.001) and IL-10 (days 3 and 10: P<0.001) whereas the post-operative levels of IL-1 beta (day 7: P<0.001; day 14: P=0.022) and TNF-alpha (day 3: P=0.006; day 7: P<0.001) were significantly higher in patients with standard enteral nutrition. CONCLUSION: Early enteral immunonutrition as compared to standard nutrition has an immunomodulative effect on the changes in the immune response after extensive surgical trauma resulting in the selective stimulation of cytokines and cytokine inhibitors. The interleukin-1 receptor antagonist is the earliest sensitive marker of anti-inflammatory response to enteral immunonutrition in malnourished patients after pancreaticoduodenectomy.