Interleukin 10 secretion in relation to human IL-10 locus haplotypes.
Stimulation of human blood cultures with bacterial lipopolysaccharide (LPS) shows large inter-individual variation in interleukin 10 (IL-10) secretion, which has been shown to have a genetic component of over 70%. Alleles at two microsatellite loci in the 4 kb immediately upstream of the human IL-10 transcription initiation site in 132 individuals from 56 Dutch families were defined and assigned as haplotypes. LPS-induced IL-10 secretion was measured by ELISA and related to the IL-10 promoter haplotypes present in 78 unrelated individuals obtained from these families. Analysis showed that LPS-induced IL-10 secretion from unrelated individuals varied with IL-10 promoter haplotypes (P = 0.024; Kruskal-Wallis test). Two observations were made in relation to secreted IL-10 levels and promoter haplotypes; first, those haplotypes containing the allele IL10.R3 were associated with lower IL-10 secretion than haplotypes containing any other IL10.R allele. Second, the haplotype IL10.R2/IL10.G14 was associated with highest IL-10 secretion overall, whereas the haplotype IL10.R3/IL10.G7 was associated with lowest IL-10 secretion. These data demonstrate that the ability to secrete IL-10 can vary in man according to the genetic composition of the IL-10 locus.
University of Glasgow Department of Surgery, Queen Elizabeth Building, Glasgow Royal Infirmary Glasgow G31 2ER, Scotland.
J
J
Eskdale
G
G
Gallagher
C L
CL
Verweij
V
V
Keijsers
R G
RG
Westendorp
T W
TW
Huizinga
D000483:Alleles; D001483:Base Sequence; D002874:Chromosome Mapping; D017931:DNA Primers; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology
D017931:DNA Primers; D008070:Lipopolysaccharides; D016753:Interleukin-10