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Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients
Peter R Lowe1, Helen F Galley, Ashraf Abdel-Fattah
1Academic Unit of Anaestesia and Intensive Care, University of Aberdeen, Scotland, UK.
Objective:
To determine the functionality of identified polymorphisms in the promoter and upstream regions of the interleukin-10 gene in terms of release of interleukin-10 from lipopolysaccharide-stimulated whole blood from healthy volunteers and to evaluate the relationship of interleukin-10 polymorphisms to interleukin-10 release, development of sepsis, and mortality in critically ill patients.
Design:
Observational study.
Setting:
The academic unit of anesthesia and intensive care, university laboratories, and ten-bed general intensive care unit in a university teaching hospital.
Subjects:
A total of 132 healthy volunteers plus 67 consecutive critically ill patients recruited within 24 hrs of admission to the intensive care unit, regardless of diagnosis.
Measurements:
Plasma interleukin-10 levels were measured by enzyme-linked immunosorbent assay. Single nucleotide polymorphisms were detected by restriction fragment length polymorphism analysis. Dinucleotide repeat polymorphisms were identified after polymerase chain reaction using a DNA size analyzer.
Main Results:
Stimulated interleukin-10 release in critically ill patients was significantly lower than in healthy subjects (p < .0001). In addition, in the patients who developed sepsis, interleukin-10 release at admission to the intensive care unit was significantly lower than in patients who did not subsequently develop sepsis (median [range] 1.47 [0.13-6.90] ng/mL compared with 4.93 [0.03-16.80] ng/mL, p = .001). The A allele of the single nucleotide polymorphism at -592 base pairs was associated with lower interleukin-10 release and higher mortality in critically ill patients. Other polymorphisms were not linked to interleukin-10 release, sepsis, or mortality.
Conclusions:
The A allele of the -592 base pair single nucleotide polymorphism in the interleukin-10 gene is associated with lower stimulated interleukin-10 release and increased mortality. Further investigations are required to determine the nature of the functionality and the potential diagnostic and therapeutic aspects of this marker.