Glucose-6-phosphate dehydrogenase deficiency and the inflammatory response to endotoxin and polymicrobial sepsis.
Crit Care Med
; 35(2): 510-8, 2007 Feb.
Article
in En
| MEDLINE
| ID: mdl-17205013
ABSTRACT
OBJECTIVE:
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common human genetic polymorphism. The deficiency protects against malaria but was shown to worsen the clinical course after severe trauma. This study tested whether the deficiency is associated with altered cytokine responses in vitro and in vivo and affects survival after endotoxemia or polymicrobial sepsis (cecal ligation and puncture).DESIGN:
Genotyping of animals was carried out using a novel and improved allele-specific polymerase chain reaction assay. Macrophage and splenocyte responses in vitro and ex vivo were compared using gene array analyses and enzyme-linked immunosorbent assays and flow cytometry under both baseline and lipopolysaccharide-stimulated conditions. Endotoxemia- or sepsis-induced mortality was compared under a variety of treatment and resuscitation protocols. SETTINGS Medical school research laboratories.SUBJECTS:
Litter mates of wild-type and G6PD-mutant mice that display a degree of G6PD deficiency similar to that observed in the African-type human deficiency (20% of normal). MEASUREMENTS AND MAINRESULTS:
Lipopolysaccharide in vivo (lipopolysaccharide from Escherichia coli, 10-35 mg/kg body weight intraperitoneally) resulted in greater interleukin-1beta, interleukin-6, and interleukin-10 levels in serum and peritoneal lavage in G6PD-deficient mice compared with wild type. Prevailing doses of lipopolysaccharide in vivo increased mortality in G6PD-deficient animals (40-70%) as compared with wild type (5-40%). In contrast, mortality after cecal ligation and puncture-induced sepsis was similar in G6PD-deficient and wild-type animals either in saline-resuscitated or antibiotic-treated animals. Splenic and blood phagocytes from septic G6PD-deficient and wild-type animals displayed attenuated ex vivo lipopolysaccharide responsiveness.CONCLUSIONS:
This study demonstrates that G6PD deficiency augments cytokine responses after inflammatory challenges. The deficiency is disadvantageous as reflected in increased mortality after hyperinflammation caused by acute endotoxemia. However, the deficiency may not manifest worsened survival after the immunosuppressed condition associated with severe sepsis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Sepsis
/
Glucosephosphate Dehydrogenase Deficiency
/
Inflammation
Type of study:
Guideline
Limits:
Animals
Language:
En
Journal:
Crit Care Med
Year:
2007
Document type:
Article
Affiliation country:
United States
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
/
US
/
USA