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.


CONCLUSIONS
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.
McDaniel
D Olga
DO
Department of Surgery, University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, USA.
Hamilton
James
J
Brock
Marjolyn
M
May
Warren
W
Calcote
Lynn
L
Tee
Lee Y
LY
Vick
Laura
L
Newman
D Brian
DB
Vick
Kenneth
K
Harrison
Sebron
S
Timberlake
Gregory
G
Toevs
Christine
C
D001741:Black or African American / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D018579:Patient Selection; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D018805:Sepsis / Q000235:genetics*; D051195:Toll-Like Receptor 2 / Q000235:genetics*; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D044465:White People / Q000235:genetics; D014947:Wounds and Injuries / Q000150:complications*
D016207:Cytokines; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4