Genetic Predisposition of the Interleukin-6 Response to Inflammation: Implications for a Variety of Major Diseases?

Author:

Bennermo Marie1,Held Claes2,Stemme Sten3,Ericsson Carl-Göran1,Silveira Angela4,Green Fiona5,Tornvall Per24

Affiliation:

1. Department of Medicine, Danderyd University Hospital, Stockholm, Sweden

2. Departments of Cardiology and

3. Department of Clinical Chemistry, Karolinska Hospital, Karolinska Institute, Stockholm, Sweden

4. Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Hospital, and

5. Department of Cardiovascular Medicine, University of Oxford and Wellcome Trust Centre for Human Genetics, Oxford, United Kingdom

Abstract

Abstract Background: A single-nucleotide polymorphism (SNP) in the promoter region of the interleukin-6 (IL-6) gene at position −174 (G>C) has been reported to be associated with a variety of major diseases, such as Alzheimer disease, atherosclerosis, and cardiovascular disease, cancer, non-insulin-dependent diabetes mellitus, osteoporosis, sepsis, and systemic-onset juvenile chronic arthritis. However, authors of previous in vitro and in vivo studies have reported conflicting results regarding the functionality of this polymorphism. We therefore aimed to clarify the role of the −174 SNP for the induction of IL-6 in vivo. Methods: We vaccinated 20 and 18 healthy individuals homozygous for the −174 C and G alleles, respectively, with 1 mL of Salmonella typhii vaccine. IL-1β, IL-6, and tumor necrosis factor-α (TNF-α) were measured in the blood at baseline and up to 24 h after vaccination. Results: Individuals with the G genotype had significantly higher plasma IL-6 values at 6, 8, and 10 h after vaccination than did individuals with the C genotype (P <0.005). There were no differences between the two genotypes regarding serum concentrations of IL-1β and TNF-α before or after vaccination. Conclusions: The −174 G>C SNP in the promoter region of the IL-6 gene is functional in vivo with an increased inflammatory response associated with the G allele. Considering the central role of IL-6 in a variety of major diseases, the present finding might be of major relevance.

Publisher

Oxford University Press (OUP)

Subject

Biochemistry (medical),Clinical Biochemistry

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