Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients.
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.


METHODS
Observational study.


METHODS
The academic unit of anesthesia and intensive care, university laboratories, and ten-bed general intensive care unit in a university teaching hospital.


METHODS
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.


METHODS
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.


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.
Lowe
Peter R
PR
Academic Unit of Anaestesia and Intensive Care, University of Aberdeen, Scotland, UK.
Galley
Helen F
HF
Abdel-Fattah
Ashraf
A
Webster
Nigel R
NR
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016638:Critical Illness / Q000401:mortality*; D005260:Female; D005819:Genetic Markers / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000097:blood / Q000235:genetics*; D008297:Male; D018895:Microsatellite Repeats; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018805:Sepsis / Q000235:genetics* / Q000401:mortality*; D018709:Statistics, Nonparametric; D015996:Survival Rate; D006113:United Kingdom / Q000453:epidemiology
D005819:Genetic Markers; D016753:Interleukin-10