Innate immunity genes influence the severity of acute appendicitis

Fernando A. Rivera-Chavez, Dixie L. Peters-Hybki, Robert C. Barber, Guy M. Lindberg, Ishwarlal Jialal, Robert S. Munford, Grant E. O'Keefe

Research output: Contribution to journalArticle

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Abstract

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. Summary Background Data: Innate immunity is the body's frontline 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-α (-308 G→A), IL-→ (-31 C →T)]. Results: Ninety-one patients (68%) had uncomplicated appendicitis and 43 (32%) had complicated disease. The SNPs in the CD14, TLR4, IL-1β, and TNF-α 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.

Original languageEnglish (US)
Pages (from-to)269-277
Number of pages9
JournalAnnals of Surgery
Volume240
Issue number2
DOIs
StatePublished - Aug 2004

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Appendicitis
Innate Immunity
Interleukin-6
Genes
Single Nucleotide Polymorphism
Inflammation
Gangrene
Ascitic Fluid
Urban Hospitals
Homozygote
Interleukin-1
Alleles
Odds Ratio
Cytokines
Wounds and Injuries
Infection

ASJC Scopus subject areas

  • Surgery

Cite this

Rivera-Chavez, F. A., Peters-Hybki, D. L., Barber, R. C., Lindberg, G. M., Jialal, I., Munford, R. S., & O'Keefe, G. E. (2004). Innate immunity genes influence the severity of acute appendicitis. Annals of Surgery, 240(2), 269-277. https://doi.org/10.1097/01.sla.0000133184.10676.26

Innate immunity genes influence the severity of acute appendicitis. / Rivera-Chavez, Fernando A.; Peters-Hybki, Dixie L.; Barber, Robert C.; Lindberg, Guy M.; Jialal, Ishwarlal; Munford, Robert S.; O'Keefe, Grant E.

In: Annals of Surgery, Vol. 240, No. 2, 08.2004, p. 269-277.

Research output: Contribution to journalArticle

Rivera-Chavez, FA, Peters-Hybki, DL, Barber, RC, Lindberg, GM, Jialal, I, Munford, RS & O'Keefe, GE 2004, 'Innate immunity genes influence the severity of acute appendicitis', Annals of Surgery, vol. 240, no. 2, pp. 269-277. https://doi.org/10.1097/01.sla.0000133184.10676.26
Rivera-Chavez FA, Peters-Hybki DL, Barber RC, Lindberg GM, Jialal I, Munford RS et al. Innate immunity genes influence the severity of acute appendicitis. Annals of Surgery. 2004 Aug;240(2):269-277. https://doi.org/10.1097/01.sla.0000133184.10676.26
Rivera-Chavez, Fernando A. ; Peters-Hybki, Dixie L. ; Barber, Robert C. ; Lindberg, Guy M. ; Jialal, Ishwarlal ; Munford, Robert S. ; O'Keefe, Grant E. / Innate immunity genes influence the severity of acute appendicitis. In: Annals of Surgery. 2004 ; Vol. 240, No. 2. pp. 269-277.
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abstract = "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. Summary Background Data: Innate immunity is the body's frontline 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-α (-308 G→A), IL-→ (-31 C →T)]. Results: Ninety-one patients (68{\%}) had uncomplicated appendicitis and 43 (32{\%}) had complicated disease. The SNPs in the CD14, TLR4, IL-1β, and TNF-α 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.",
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AU - Peters-Hybki, Dixie L.

AU - Barber, Robert C.

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AU - Jialal, Ishwarlal

AU - Munford, Robert S.

AU - O'Keefe, Grant E.

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AB - 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. Summary Background Data: Innate immunity is the body's frontline 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-α (-308 G→A), IL-→ (-31 C →T)]. Results: Ninety-one patients (68%) had uncomplicated appendicitis and 43 (32%) had complicated disease. The SNPs in the CD14, TLR4, IL-1β, and TNF-α 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.

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