Innate immunity genes influence the severity of acute appendicitis.
OBJECTIVE
Using acute appendicitis as a model, we tested the hypothesis that polymorphisms in genes involved in host defense can be associated with the severity of local infection-inflammation in humans.


BACKGROUND
Innate immunity is the body's front-line system for antimicrobial host defense. Local inflammation is a major innate immune mechanism for containing and destroying microbes, but it may also contribute to tissue injury.


METHODS
We studied 134 patients with acute appendicitis treated at an urban hospital. We looked for associations between the severity of appendicitis (uncomplicated vs. perforated or gangrenous), plasma and peritoneal cytokine concentrations, and single nucleotide polymorphisms in genes involved in recognizing bacterial molecules [CD14 (-159 C-->T); TLR4 (896 A-->G)] and in mounting an inflammatory response [IL-6 (-174 G-->C), TNF-alpha (-308 G-->A), IL-1beta (-31 C -->T)].


RESULTS
Ninety-one patients (68%) had uncomplicated appendicitis and 43 (32%) had complicated disease. The SNPs in the CD14, TLR4, IL-1beta, and TNF-alpha genes were not associated with the severity of appendicitis. A strong association was found between C-allele carriage at -174 in the IL-6 gene and decreased risk of complicated disease (adjusted odds ratio = 0.24, 95% CI = 0.07-0.76). Lower plasma and peritoneal fluid IL-6 concentrations in the IL-6 -174 C-carriers than in the GG homozygotes suggest that this polymorphism contributes to decreased IL-6 production in vivo.


CONCLUSIONS
Polymorphism in the IL-6 gene was associated with the severity of appendicitis, even after adjustment for duration of symptoms. The risk for developing appendiceal perforation or gangrene may be determined, in part, by variation in the IL-6 gene.
Department of Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Fernando A
FA
Rivera-Chavez
Dixie L
DL
Peters-Hybki
Robert C
RC
Barber
Guy M
GM
Lindberg
Ishwarlal
I
Jialal
Robert S
RS
Munford
Grant E
GE
O'Keefe
D000208:Acute Disease; D000328:Adult; D001062:Appendectomy / Q000379:methods; D001064:Appendicitis / Q000235:genetics* / Q000276:immunology / Q000601:surgery; D001483:Base Sequence; D015331:Cohort Studies; D016001:Confidence Intervals; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005819:Genetic Markers; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics*; D018836:Inflammation Mediators / Q000032:analysis; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D016896:Treatment Outcome
D005819:Genetic Markers; D018836:Inflammation Mediators; D015850:Interleukin-6