Alleles carried at positions ?819 and ?592 of the IL10 promoter affect transcription following stimulation of peripheral blood cells with Streptococcus pneumoniae

• DOI: 10.1007/s00251-003-0621-6
• Publication Date: 2004-03-19T05:00:55Z
• Authors: Suzanna E. L. Temple; Esther Lim; Karey Y. Cheong; Coral-Ann M. Almeida; Patricia Price; Kristin G. Ardlie; Grant W. Waterer
• Keywords: Adult; Lipopolysaccharides; Male; 0301 basic medicine; Polymorphism, Genetic; Transcription, Genetic; Homozygote; Middle Aged; Interleukin-10; 3. Good health; 03 medical and health sciences; Streptococcus pneumoniae; Haplotypes; Leukocytes, Mononuclear; Humans; Female; RNA, Messenger; Promoter Regions, Genetic; Alleles

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.