Molecular analysis of inflammatory markers in trauma patients at risk of postinjury complications

J Trauma. 2007 Jul;63(1):147-57; discussion 157-8. doi: 10.1097/TA.0b013e31806bf0ab.

Abstract

Background: Genetic differences associated with individual's immune responses appear to be a major contributing factor to the development of trauma- induced sepsis. Thus, effective treatment of sepsis requires the identification of the patients who are at increased risk for sepsis.

Methods: Sixty-eight patients, of which the majority had an injury severity score >15, and 118 controls from the same geographic region were genotyped. Cytokine and Toll-like receptor (TLR) genotypes and expressions were tested using polymerase chain reaction (PCR).

Results: Fifty percent of African American and 42% of Caucasian patients developed posttrauma sepsis. Frequency distribution of the polymorphism for some cytokine genes such as Interleukin (IL)-10 low/high and interferon (IFN)-gamma low producer were statistically different between the septic and aseptic patients, for others, such as tumor necrosis factor (TNF)-alpha, IL-6, and IL-18, there was no statistical difference. The TLR-2 genotypes (A/G) were considered a sepsis risk marker as compared with A/A (62.5% versus 37.5%, p < 0.03; relative risk = 2.5) in African American patients. Cytokine mRNA levels correlated with genotype definition, particularly, for IL-10, IL-6, IL-18, and TNF-alpha. A time course study demonstrated a significant difference in cytokines expression profile in septic and aseptic patients before the development of sepsis.

Conclusion: Monitoring cytokine expression levels before the disease might predict the outcome of sepsis. A large cohort study is needed to assess the diagnostic potential of the genotypes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Black or African American / genetics
  • Cytokines / genetics*
  • Gene Frequency
  • Genotype
  • Humans
  • Injury Severity Score
  • Male
  • Patient Selection
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Sepsis / genetics*
  • Toll-Like Receptor 2 / genetics*
  • Toll-Like Receptor 4 / genetics*
  • White People / genetics
  • Wounds and Injuries / complications*

Substances

  • Cytokines
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4