Interleukin-10-1082 promoter polymorphism in association with cytokine production and sepsis susceptibility.
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.


METHODS
Case-control study.


METHODS
Research laboratory of Molecular Biology and Immunology and University Hospital ICU, Faculty of Medicine, Trakia University.


METHODS
A total of 53 healthy volunteers and 33 patients in ICU meeting the criteria for severe sepsis were included.


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.


CONCLUSIONS
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.
Stanilova
Spaska A
SA
Faculty of Medicine, Department of Molecular Biology, Immunology and Genetics, Trakia University, Armeiska 11 St., 6000, Stara Zagora, Bulgaria. stanilova@mf.uni-sz.bg.
Miteva
Lyuba D
LD
Faculty of Medicine, Department of Molecular Biology, Immunology and Genetics, Trakia University, Armeiska 11 St., 6000, Stara Zagora, Bulgaria.
Karakolev
Zhivko T
ZT
Department of Intensive Medicine and ICU, Faculty of Medicine, Trakia University, Stara Zagora, Bulgaria.
Stefanov
Chavdar S
CS
Department of Anesthesiology and Intensive care, Medical University, Plovdiv, Bulgaria.
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D018805:Sepsis / Q000235:genetics*; D018709:Statistics, Nonparametric
D016753:Interleukin-10