Molecular Analysis of Inflammatory Markers in Trauma Patients at Risk of Postinjury Complications

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.