The IL-10 -819T polymorphism is associated with increased susceptibility to severe sepsis
© BioMed Central Ltd 2003
Published: 3 March 2003
Severe sepsis is characterized by an aggressive inflammatory response, and is more common in patients with genetic polymorphisms that promote greater production of pro-inflammatory cytokines (e.g. -308A on the TNF gene). Thus, we hypothesized that the genetic predisposition to lesser anti-inflammatory response (-819T on the IL-10 gene) would also increase the risk of severe sepsis.
As part of a first interim analysis of an ongoing NIH-sponsored multicenter study of Genetic and Inflammatory Markers of Sepsis (GenIMS), we analyzed 284 adult patients presenting to the Emergency Department (ED) with community-acquired pneumonia (CAP). We drew blood from patients presenting to EDs in southwest Pennsylvania with CAP for genotyping and plasma IL-10 levels. We defined severe sepsis as a Sequential Organ Failure Assessment Score increase of 2 for any one nonrespiratory organ, or an increase of 1 for any two nonrespiratory organs, or an absolute score of 3 or 4 for respiratory organs.
The cohort had a mean age of 66.9 ± 17.1 years; 49.6% were female; 87.7% were Caucasian; 30.3% had underlying respiratory disease; and 39.4% developed severe sepsis. Subjects with either genotype C/T or T/T at IL-10 -819 were associated with a greater risk of progression to severe sepsis compared with the common homozygote C/C (odds ratio = 1.71, P = 0.03). We did not find a consistent difference in plasma IL-10 levels in subjects with different genotypes.
IL-10 -819 polymorphisms
% severe sepsis
Supported by NIH grant R01 GM61992-01.