Association of IL-8-251A/T polymorphism with incidence of Acute Respiratory Distress Syndrome (ARDS) and IL-8 synthesis after multiple trauma.
BACKGROUND
Interleukin-8 (IL-8) is regarded as one of the most important mediators in the pathogenesis of Adult Respiratory Distress Syndrome (ARDS). However, knowledge regarding the influence of genetic variations within the IL-8 gene either on the development of ARDS or on IL-8 production in the traumatic setting is sparse.


METHODS
In this prospective cohort study, patients were included if the following criteria were fulfilled: Injury Severity Score (ISS) >16, age 18-60 years and a survival >48 h after injury. Systemic IL-8 concentrations and the polymorphisms (IL-8-251A/T) were determined. Patients were separated according to the development of ARDS (group +ARDS vs. group -ARDS) and the genotypes of the IL-8-251A/T polymorphism (genotypes A/A, A/T and T/T).


RESULTS
Group +ARDS demonstrated significantly higher IL-8 plasma concentrations from day 3 until the end of the observation period compared to group -ARDS. In addition, duration of mechanical ventilation and length of stay in the ICU were significantly longer in this group. Furthermore, a significant association between the IL-8-251A allele and IL-8 production (day 4-8) was observed. Genotype A/A showed a significantly longer duration of mechanical ventilation compared to genotype T/T. A trend towards an association between the IL-8-251A allele and an increased incidence of posttraumatic ARDS was observed (p=0.08).


CONCLUSIONS
This data reaffirms a central role of IL-8 in the pathogenesis of ARDS. Furthermore, it points towards a genetic predisposition for posttraumatic IL-8 synthesis which might also be associated with the development of posttraumatic ARDS.
Hildebrand
Frank
F
Trauma Department, Medical School Hannover, Carl-Neuberg Strasse 1, 30625 Hannover, Germany. Hildebrand.Frank@mh-hannover.de
Stuhrmann
Manfred
M
van Griensven
Martijn
M
Meier
Sven
S
Hasenkamp
Sandra
S
Krettek
Christian
C
Pape
Hans-Christoph
HC
D000328:Adult; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009104:Multiple Trauma / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000235:genetics*
D016209:Interleukin-8