The IL-10 -819T polymorphism is associated with increased susceptibility to severe sepsis

Introduction

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.

Methods

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.

Results

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.

Conclusion

In this preliminary analysis of subjects with CAP, those with the IL-10 -819 C/T or T/T genotypes are more likely to develop severe sepsis compared with those with the usual homozygous C/C phenotype.

Table 1 IL-10 -819 polymorphisms