Genetic polymorphisms in the promoter region of interleukin-8

In septic patients, local and systemic production of interleukin-8 (IL-8) is augmented, and we and other researchers have previously shown that serum IL-8 levels predict the development of multiple organ dysfunction syndrome (MODS) and poor prognosis. There is a wide variation in IL-8 levels among septic patients under similar conditions and this is, at least, partly due to the genetic variability, in addition to the differences in predisposing stimuli. Thus, in the present study, we examined single nucleotide polymorphisms (SNPs), which may affect the production of IL-8. After obtaining informed consent, we draw 10 ml of heparinized blood and extracted DNA. We initially sequenced the 300-bp promoter region of the IL-8 gene in 25 Japanese healthy volunteers and confirmed one SNP at position −251, which was identical to the previously reported SNP in Caucasians. By further analysis of IL-8 genotype by RT-PCR in 100 Japanese healthy volunteers, the genotype distribution (A/A:A/T:T/T) was 16:47:37, suggesting the similar IL-8 genotype distribution between Japanese and Caucasians. We then examined the IL-8 genotype in 10 septic patients as a preliminary study and it was 1:3:6. Additional experiments are ongoing to determine its significance.