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Interleukin 10 secretion in relation to human IL-10 locus haplotypes
J Eskdale1, G Gallagher, C L Verweij
1University of Glasgow Department of Surgery, Queen Elizabeth Building, Glasgow Royal Infirmary Glasgow G31 2ER, Scotland.
Summary
Genetic variations in the interleukin 10 (IL-10) promoter influence how much IL-10 is secreted in response to bacterial lipopolysaccharide (LPS). Specific IL-10 promoter haplotypes are linked to both higher and lower IL-10 secretion levels.
Area of Science:
- Immunogenetics
- Molecular genetics
- Human genetics
Background:
- Inter-individual variation in interleukin 10 (IL-10) secretion following bacterial lipopolysaccharide (LPS) stimulation is significant.
- This variation has a substantial genetic component, estimated at over 70%.
Purpose of the Study:
- To investigate the relationship between genetic variations in the IL-10 promoter region and LPS-induced IL-10 secretion.
- To identify specific IL-10 promoter haplotypes associated with varying levels of IL-10 secretion.
Main Methods:
- Analysis of microsatellite loci and haplotype definition in the IL-10 promoter region of Dutch families.
- Measurement of LPS-induced IL-10 secretion using ELISA in unrelated individuals.
- Statistical analysis (Kruskal-Wallis test) to correlate IL-10 promoter haplotypes with IL-10 secretion levels.
Main Results:
- Significant variation in LPS-induced IL-10 secretion was observed among individuals with different IL-10 promoter haplotypes (P = 0.024).
- Haplotypes containing the IL10.R3 allele were associated with lower IL-10 secretion compared to other IL10.R alleles.
- The IL10.R2/IL10.G14 haplotype showed the highest overall IL-10 secretion, while IL10.R3/IL10.G7 showed the lowest.
Conclusions:
- The genetic makeup of the IL-10 locus significantly influences an individual's capacity to secrete IL-10.
- Specific IL-10 promoter haplotypes can predict varying levels of IL-10 response to LPS stimulation.