Associations between TNF-α, IL-6 and IL-10 Promoter Polymorphisms and Mortality in Severe Sepsis
Olegs Sabelnikovs
Departments of Anesthesiology and Reanimatology, Riga Stradins University and Pauls Stradins Clinical University Hospital, Riga, Latvia.
Liene Nikitina-Zake
Latvian Biomedical Research and Study Centre, Genome Centre, Riga, Latvia.
Angelika Krumina
Department of Infectology and Dermatology, Riga Stradins University, Riga, Latvia.
Zane Jaunberga
Departments of Anesthesiology and Reanimatology, Riga Stradins University and Pauls Stradins Clinical University Hospital, Riga, Latvia.
Janis Klovins
Latvian Biomedical Research and Study Centre, Genome Centre, Riga, Latvia.
Ludmila Viksna
Department of Infectology and Dermatology, Riga Stradins University, Riga, Latvia.
Lars J. Bjertnaes
Department of Clinical Medicine (Anesthesiology), Medical Faculty, University of Tromsø and Department of Anesthesiology, University Hospital of North Norway, Tromsø, Norway.
Lilija Kovalchuka *
Riga Stradins University, Clinical Immunology and Immunogenetic laboratory, Riga, Latvia.
Indulis Vanags
Departments of Anesthesiology and Reanimatology, Riga Stradins University and Pauls Stradins Clinical University Hospital, Riga, Latvia.
*Author to whom correspondence should be addressed.
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.
Keywords: Sepsis, TNF-α, IL-6, IL-10, polymorphisms, allele, PCR, SNP