IL-18 promoter polymorphisms correlate with the development of post-injury sepsis.
BACKGROUND
Interleukin (IL)-18 is a proinflammatory cytokine involved in the regulation of cell-mediated and innate immune responses to infection, trauma, and inflammation. Elevated levels of IL-18 have been noted to correlate with organ dysfunction after injury. This study evaluates the relationship between IL-18 promoter polymorphisms and the development of sepsis after injury.


METHODS
DNA was extracted from peripheral leukocytes of trauma patients with an injury severity score of 16 or greater. Patient clinical course was followed for the development of sepsis as an endpoint. Two SNPs (-607bp and -137bp) were amplified using polymerase chain reaction. Alleles were identified via agarose gel separation. Genotypes were then determined and correlated with patient data. Postinjury IL-18 levels were determined by enzyme-linked immunoassay.


RESULTS
Sixty-six patients were evaluated; 36 (52%) developed sepsis. Each SNP had 2 alleles and 3 genotypes. The SNP at -607bp had an allelic frequency of 59% for C and 41% for A; whereas -137bp was a G 79% of the time and a C 21% of the time. Individually, each SNP had no direct correlation between the patient's genotype and development of infection. However, when the -607bp CA genotype was combined with the -137bp GC genotype (CA/GC), only 4 patients (27%) developed sepsis (P =.02).


CONCLUSIONS
This study supports the conclusion that IL-18 genetic promoter polymorphisms correlate with the development of postinjury sepsis. Further investigation is needed to identify the impact of variation in genotype across a range of genes involved in connected regulatory pathways.
Stassen
Nicole A
NA
Department of Surgery, Price Institute of Surgical Research, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Breit
Christina M
CM
Norfleet
Lisa A
LA
Polk
Hiram C
HC
D000328:Adult; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007239:Infections / Q000209:etiology*; D020382:Interleukin-18 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014947:Wounds and Injuries / Q000150:complications* / Q000235:genetics*
D020382:Interleukin-18