Session X - Polytrauma II

Sat., 10/22/05 Polytrauma II, Paper #42, 9:06 am

Posttraumatic Alterations of the Immune Response: Is There a Genetic Predisposition?

Frank Hildebrand, MD (a-Grant, Hannover Medical School);
Martijn van Griensven, MD (n); Christian Krettek, MD (n);
Hans-Christoph Pape, MD (n);
Trauma Department, Hanover Medical School, Hannover, Germany

Introduction: Severe trauma induces sustained changes of the immune response. Despite a similar injury severity, the extent of the inflammatory response may vary among polytraumatized patients. It is unclear whether a inflammatory variability is associated with genetic variations.

Methods: In this prospective cohort study, polytraumatized patients were consecutively included. Inclusion criteria were Injury Severity Score (ISS) >16, age 18 to 60 years, and survival >48 hours. During a 14-day observation period, blood samples were drawn once daily for systemic cytokine concentrations (TNF-a, IL-1ß, IL-6, IL-8, and IL-10). Eight different polymorphisms at 5 different loci were examined. The clinical course was recorded once daily. For analysis of allele frequencies, genotype distribution, and cytokine concentrations, polytraumatized patients were separated according to the severity of systemic inflammatory response syndrome (SIRS)2 SIRS criteria in group SIRS- and >2 SIRS criteria in group SIRS+.

Results: 97 severely injured patients were included in this study (41 patients in SIRS+ and 56 in the SIRS- group). The genotypic distribution of SNPs demonstrated significant differences for the IL-6-174G/C. IL-6 concentrations were significantly higher in SIRS+ patients at day 1 and between days 4 and 8. The G/G genotype of the IL-6 polymorphism was associated with significantly higher IL-6 concentrations compared to the C/C genotype from day 5 to 8. Furthermore, IL-8 concentrations were significantly higher from day 1 to 4 in SIRS+ patients. Significantly higher IL-8 concentrations were observed in the A/A genotype group compared to the T/T genotype. A trend towards an association between the IL-8-251A/T polymorphism and the development of acute respiratory distress syndrome was demonstrated (p=0.06). No differences in plasma concentrations of TNF-a, IL-1ß, and IL-10 or in the genotypic distribution of TNF-a, IL-1ß, and IL-10 polymorphisms were observed.


Discussion: In polytraumatized patients, the IL-6-174G/C polymorphism appears to be associated with the severity of posttraumatic SIRS and with significantly higher systemic IL-6 plasma concentrations. Furthermore, significantly higher IL-8 concentrations were observed in the genotype A/A. A genetic predisposition towards an enhanced inflammatory response after severe blunt trauma may occur and may be associated with adverse outcome. This study warrants further investigation in regards to the genetic background of the systemic inflammatory reaction.

If noted, the author indicates something of value received. The codes are identified as a-research or institutional support; b-miscellaneous funding; c-royalties; d-stock options; e-consultant or employee; n-no conflicts disclosed, and *disclosure not available at time of printing.