Interleukin-10 haplotype associated with increased mortality in critically ill patients with sepsis from pneumonia but not in patients with extrapulmonary sepsis

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.