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 μg/ml) or heat-killed Streptococcus pneumoniae (107cfu/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.