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(Chest. 2005;128:1690-1698.)
© 2005 American College of Chest Physicians

Interleukin-10 Haplotype Associated With Increased Mortality in Critically Ill Patients With Sepsis From Pneumonia But Not in Patients With Extrapulmonary Sepsis*

Anan Wattanathum, MD; Sanjay Manocha, MD; Horacio Groshaus, MD; James A. Russell, MD and Keith R. Walley, MD

* From the Critical Care Research Laboratories, University of British Columbia, Vancouver, BC, Canada.

Correspondence to: Keith R. Walley, MD, Critical Care Research Laboratories, 1081 Burrard St, Vancouver, BC, Canada V6Z 1Y6; e-mail: kwalley{at}mrl.ubc.ca

Study objective: To test the hypothesis that haplotypes of the interleukin (IL)-10 gene are associated with clinical outcomes, comparing critically ill patients with sepsis from pneumonia vs those with extrapulmonary sepsis.

Design: Genetic association study.

Setting: Medical/surgical ICUs in a tertiary-care, university-affiliated teaching hospital.

Patients: Of 550 white patients with sepsis, 158 had pneumonia as the principle cause of their sepsis and 392 had an extrapulmonary source of sepsis.

Measurements: Haplotypes of the IL-10 gene were defined by measurement of haplotype tag single-nucleotide polymorphisms (SNPs). Primary outcome was 28-day survival. Secondary outcomes were days alive and free of organ dysfunction.

Results: Three SNPs in the IL-10 gene (– 592 C/A, + 734 G/T, and + 3367 G/A) identified four major haplotypes: CGG, AGG, CTA, and CTG. Patients with pneumonia who carried one or two copies of the CGG haplotype had greater 28-day mortality (51.4%) than patients who did not carry this haplotype (29.1%, p = 0.007). Carriers of CGG had significantly more cardiovascular dysfunction (and use of vasopressors), renal dysfunction (and requirement of dialysis), hepatic dysfunction, and hematologic dysfunction (p < 0.05 in each case). In contrast, in patients with an extrapulmonary source of infection there was no significant association of the CGG haplotype (or any measured IL-10 genotype) with 28-day mortality or organ dysfunction.

Conclusions: The IL-10 haplotype – 592C/734G/3367G is associated with increased mortality and organ dysfunction in critically ill patients with pulmonary sepsis but not in similarly ill patients with extrapulmonary sepsis. Therefore, polymorphisms within the IL-10 gene may be predictors of outcome in patients with sepsis from pneumonia.

Key Words: haplotype • interleukin-10 • pneumonia • polymorphism • sepsis • 28-day mortality






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