However, there is no selleck chemical association for the -819 polymorphism. Our results are in agreement with previous reports [15,34], but in contrast to the results reported by Keijsers and colleagues [36] and Rad and colleagues [37]. They showed that the A allele at -1082 and the T allele at -819 were associated with higher and lower IL-10 production, respectively. Similar to their effect on transcription, LPS-stimulating production of IL-10 by peripheral blood leukocytes is lowest in patients with combined genotype 2 ATA, which is significantly different compared with patients with genotype 0 ATA. The ATA haplotype has been demonstrated to have lowest transcriptional activity [19]. Our results further confirm the functionality of the IL-10 promoter SNPs in relation to IL-10 production.
It also suggests that individual differences in IL-10 production in trauma patients might be at least in part related to genetic variations in the IL-10 promoter region.Given the functional significance of the -1082 and -592 polymorphisms and ATA haplotype, we further hypothesized that the IL-10 promoter polymorphisms would be important in influencing severity to the development of sepsis and MODS in trauma patients by changing the balance of pro-inflammatory and anti-inflammatory cytokines. There were no significant differences in age, gender ratio and ISS scores among the different genotype groups, which minimized the influence of interfering factors. The patient cohort consisted of young patients with a low background of coexisting morbidity.
Similar to their association with IL-10 production, genetic variations at the three loci have a trend to be associated with lower risk of sepsis and MODS. However, only the -1082 polymorphism has statistical significance, showing that the patients with the A allele had significantly higher sepsis morbidity and a borderline significant increase in MODS scores. There are also significant differences in the frequencies of the allele and AA genotype at this polymorphic locus between patients with sepsis and non-sepsis. The finding of no significant difference in the GG genotype frequency might be due to a small number of patients carrying the GG genotype in the current study. Results from Stanilova and colleagues [22] also revealed that the AA genotype of the -1082 locus was associated with lower IL-10 production in LPS-, phytohemagglutinin- or pokeweed mitogen-stimulated healthy peripheral blood leukocytes. Patients with severe sepsis were shown to have a significant elevation of A allele frequency when compared with healthy controls. In addition, Gong and colleagues [21] further reported Anacetrapib that the high IL-10-producing -1082 GG genotype was protective against organ failure and mortality in acute respiratory distress syndrome.