Interleukin-10-1082 promoter polymorphism in association with cytokine production and sepsis susceptibility
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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.
Research laboratory of Molecular Biology and Immunology and University Hospital ICU, Faculty of Medicine, Trakia University.
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.
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.
KeywordsInterleukin-10 Polymorphism Severe sepsis
- 18.Shu Q, Fang X, Chen Q, Stuber F (2003) IL-10 polymorphism is associated with increased incidence of severe sepsis. Chin Med J (Engl) 116:1756–1759Google Scholar
- 21.Cavet J, Middleton P, Segal M, Noreen H, Davies S, Dickinson A (1999) Recipient tumor necrosis factor and interleukin-10 gene polymorphisms associate with early mortality and acute graft-versus-host disease severity in HLA-matched sibling bone marrow transplants. Blood 94:3941–3946PubMedGoogle Scholar
- 23.Crawley E, Kay R, Sillibourne J, Patel P, Hutchinson I, Woo P (1999) Polymorphic haplotypes of the interleukin-10 5′ flanking region determine variable interleukin-10 transcription and are associated with particular phenotypes of juvenile rheumatoid arthritis. Arthritis Rheum 42:1101–1108CrossRefPubMedGoogle Scholar
- 24.Paterson JCM (1999) Inherited haplotypes of the interleukin-10 promoter differentially regulate gene transcription. Joint Congress of the BSI and the BSACI, abstract OP258Google Scholar
- 26.Keijsers V, Verweij CL, Hazes JMW, Westendorp RGJ, Breedveld FC, Huizinga TWJ (1998) Innate differences in IL-10 production are present at the level of transcription and associated with haplotypes: association of IL-10 haplotypes and rheumatoid arthritis. Clin Exp Rheumatol 16:200Google Scholar