Spaska A Stanilova1, Lyuba D Miteva2, Zhivko T Karakolev3, Chavdar S Stefanov4. 1. Faculty of Medicine, Department of Molecular Biology, Immunology and Genetics, Trakia University, Armeiska 11 St., 6000, Stara Zagora, Bulgaria. stanilova@mf.uni-sz.bg. 2. Faculty of Medicine, Department of Molecular Biology, Immunology and Genetics, Trakia University, Armeiska 11 St., 6000, Stara Zagora, Bulgaria. 3. Department of Intensive Medicine and ICU, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria. 4. Department of Anesthesiology and Intensive care, Medical University, Plovdiv, Bulgaria.
Abstract
OBJECTIVE: To investigate the -1082 (A/G) polymorphism in the promoter of the IL-10 gene in terms of IL-10 production from stimulated peripheral blood mononuclear cells (PBMC) and to evaluate the relationship of this polymorphism with susceptibility to severe sepsis and the outcome of the disease. DESIGN: Case-control study. SETTING: Research laboratory of Molecular Biology and Immunology and University Hospital ICU, Faculty of Medicine, Trakia University. PATIENTS: A total of 53 healthy volunteers and 33 patients in ICU meeting the criteria for severe sepsis were included. MEASUREMENTS AND RESULTS: The amplification refractory mutation system PCR was used for IL-10-1082 polymorphism detection. Isolated PBMC were stimulated with either C3-binding glycoprotein (C3bgp), lipopolysaccharide (LPS), phytohemagglutinin (PHA),or pokeweed mitogen (PWM). IL-10 production was measured in culture supernatants. The AA genotype was associated with lower IL-10 production in LPS-, PHA- or PWM-stimulated healthy PBMC. Patients with severe sepsis had significant elevation of A allele, compared with healthy controls (74.2% vs 52.8%; p=0.0062). Carriage of at least one copy of IL-10-1082 G allele in sepsis patients and in healthy controls resulted in a statistically significant increase in IL-10 production from stimulated PBMC. Surviving sepsis patients had a significant decrease of IL-10-1082 allele G frequency, compared with controls (17% vs 47.2%; p=0.012). An association between increased IL-10 production and poor outcome from sepsis was observed. CONCLUSION: The A allele of the -1082 polymorphism in the interleukin-10 gene promoter is associated with sepsis susceptibility, whereas G allele is associated with higher stimulated interleukin-10 production and increased mortality in severe sepsis.
OBJECTIVE: To investigate the -1082 (A/G) polymorphism in the promoter of the IL-10 gene in terms of IL-10 production from stimulated peripheral blood mononuclear cells (PBMC) and to evaluate the relationship of this polymorphism with susceptibility to severe sepsis and the outcome of the disease. DESIGN: Case-control study. SETTING: Research laboratory of Molecular Biology and Immunology and University Hospital ICU, Faculty of Medicine, Trakia University. PATIENTS: A total of 53 healthy volunteers and 33 patients in ICU meeting the criteria for severe sepsis were included. MEASUREMENTS AND RESULTS: The amplification refractory mutation system PCR was used for IL-10-1082 polymorphism detection. Isolated PBMC were stimulated with either C3-binding glycoprotein (C3bgp), lipopolysaccharide (LPS), phytohemagglutinin (PHA),or pokeweed mitogen (PWM). IL-10 production was measured in culture supernatants. The AA genotype was associated with lower IL-10 production in LPS-, PHA- or PWM-stimulated healthy PBMC. Patients with severe sepsis had significant elevation of A allele, compared with healthy controls (74.2% vs 52.8%; p=0.0062). Carriage of at least one copy of IL-10-1082 G allele in sepsispatients and in healthy controls resulted in a statistically significant increase in IL-10 production from stimulated PBMC. Surviving sepsispatients had a significant decrease of IL-10-1082 allele G frequency, compared with controls (17% vs 47.2%; p=0.012). An association between increased IL-10 production and poor outcome from sepsis was observed. CONCLUSION: The A allele of the -1082 polymorphism in the interleukin-10 gene promoter is associated with sepsis susceptibility, whereas G allele is associated with higher stimulated interleukin-10 production and increased mortality in severe sepsis.
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