Alleles carried at positions -819 and -592 of the IL10 promoter affect transcription following stimulation of peripheral blood cells with Streptococcus pneumoniae.
IL-10 inhibits the production of many pro-inflammatory cytokines. Polymorphisms in the IL10 gene promoter at positions -1082G-->A, -819C-->T and -592C-->A occur as three haplotypes, ATA, GCC and ACC. These influence several infectious and inflammatory diseases including community-acquired pneumonia, where a role for IL-10 is suggested by fluctuations in plasma levels of the cytokine. However, the effects of the haplotypes on IL-10 production are unclear. We stimulated peripheral blood mononuclear cells (PBMC) from at least five individuals homozygous for each of the three haplotypes with lipopolysaccharide (LPS, 10 microg/ml) or heat-killed Streptococcus pneumoniae (10(7)cfu/ml) and measured IL-10 mRNA by RT-PCR. Following S. pneumoniae stimulation, PBMC with the ATA haplotype had higher IL-10 mRNA levels than those with the GCC haplotype at 4 h (independent t-test; P=0.024), or the ACC haplotype at 4 h ( P<0.0001) and 8 h ( P=0.007). Following LPS stimulation, IL-10 mRNA levels were not significantly influenced by the IL10 haplotype, but similar trends were observed, consistent with the variable outcome of published studies. The results suggest that the -819 and/or -592 alleles affect transcription.
Temple
Suzanna E L
SE
School of Medicine and Pharmacology, Royal Perth Hospital, University of Western Australia, GPO Box X2213, WA 6847, Perth, Australia. setemple@cyllene.uwa.edu.au
Lim
Esther
E
Cheong
Karey Y
KY
Almeida
Coral-Ann M
CA
Price
Patricia
P
Ardlie
Kristin G
KG
Waterer
Grant W
GW
D000328:Adult; D000483:Alleles; D005260:Female; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D014158:Transcription, Genetic
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10