Associations between TNF-α, IL-6 and IL-10 Promoter Polymorphisms and Mortality in Severe Sepsis

Abstract

Aims: To determine whether an association exists between TNF-α 308 A/G, IL-6 174 G/C, and IL-10-1082 A/G promoter polymorphisms and the corresponding systemic cytokine concentrations and outcome in patients suffering from sepsis. Place and Duration of Study: The study was performed in the Intensive Care Unit (ICU) of Pauls Stradins Clinical University Hospital, Riga. Between 1 August 2006 and 31 July 2008. Methodology: We enrolled 103 consecutive intensive care unit patients with sepsis into a prospective case control study. Blood samples were obtained for extraction of DNA amplifying regions of interest by means of polymerase chain reaction technique (PCR) using specific primers for TNF-α, IL-6 and IL-10. Simultaneously, plasma cytokines and standard laboratory variables were determined during the first 24 h after the diagnosis. Presence of septic shock, sequential organ failure assessment score (SOFA), demographic data and clinical outcome was noticed P < 0.05 was considered as statistically significant. Results: Non-survivors had significantly higher concentrations of TNF-α, IL-6 and IL-10. The carriage of the IL-6-174C allele and IL-10 -1082G allele were associated with a higher risk of mortality in patients with severe sepsis. Presence of the TNF-α -308 A allele did not influence mortality differently from those lacking this allele. Conclusion: The present study demonstrated an association of the IL-6 -174 and the IL-10 -1082 with increased mortality in patients suffering from severe sepsis. We found no direct association between the examined polymorphisms and the corresponding cytokine levels.