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

Peter Lowe, Helen Frances Galley, A. Abdel-Fattah, Nigel Robert Webster

Research output: Contribution to journalArticle

133 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)34-38
Number of pages4
JournalCritical Care Medicine
Volume31
Issue number1
DOIs
Publication statusPublished - 2003

Keywords

  • interleukin-10
  • polymorphism
  • mortality
  • sepsis
  • SYSTEMIC-LUPUS-ERYTHEMATOSUS
  • NECROSIS-FACTOR-ALPHA
  • SEPTIC SHOCK
  • 5'-FLANKING REGION
  • GENE PROMOTER
  • TNF-ALPHA
  • INFLAMMATORY RESPONSE
  • MENINGOCOCCAL DISEASE
  • RHEUMATOID-ARTHRITIS
  • DINUCLEOTIDE REPEAT

Cite this

Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients. / Lowe, Peter; Galley, Helen Frances; Abdel-Fattah, A.; Webster, Nigel Robert.

In: Critical Care Medicine, Vol. 31, No. 1, 2003, p. 34-38.

Research output: Contribution to journalArticle

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title = "Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients",
abstract = "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.",
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author = "Peter Lowe and Galley, {Helen Frances} and A. Abdel-Fattah and Webster, {Nigel Robert}",
year = "2003",
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TY - JOUR

T1 - Influence of interleukin-10 polymorphisms on interleukin-10 expression and survival in critically ill patients

AU - Lowe, Peter

AU - Galley, Helen Frances

AU - Abdel-Fattah, A.

AU - Webster, Nigel Robert

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

KW - interleukin-10

KW - polymorphism

KW - mortality

KW - sepsis

KW - SYSTEMIC-LUPUS-ERYTHEMATOSUS

KW - NECROSIS-FACTOR-ALPHA

KW - SEPTIC SHOCK

KW - 5'-FLANKING REGION

KW - GENE PROMOTER

KW - TNF-ALPHA

KW - INFLAMMATORY RESPONSE

KW - MENINGOCOCCAL DISEASE

KW - RHEUMATOID-ARTHRITIS

KW - DINUCLEOTIDE REPEAT

U2 - 10.1097/00003246-200301000-00005

DO - 10.1097/00003246-200301000-00005

M3 - Article

VL - 31

SP - 34

EP - 38

JO - Critical Care Medicine

JF - Critical Care Medicine

SN - 0090-3493

IS - 1

ER -