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. 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.