title: The effect of hyperglycemia on neonatal immune responses in-vitro.
abstract: BACKGROUND
  Acute hyperglycemia is considered as a pro-inflammatory state and is related to an adverse outcome in critically ill adults. Neonates are susceptible to infections and systemic inflammatory response syndrome induced by pro-inflammatory cytokines. This study focuses on the interaction between neonatal glucose homeostasis and the pro-inflammatory cytokine production in term and preterm infants in-vitro.
  
  
  METHODS
  We analyzed the pro-inflammatory cytokine production in whole cord blood of term infants (n = 10), preterm infants > 32 weeks (n=16) and preterm infants ≤32 weeks of gestational age (n = 13) and in adult controls (n=14) using an in-vitro sepsis-model. Whole blood was pre-incubated with different concentrations of glucose (0-1000 mg/dl) and insulin (0-62.5 IE/l) and stimulated with lipopolysaccharide. The intracytoplasmatic TNF-α, IL-6, and IL-8 response was measured by flow cytometry.
  
  
  RESULTS
  In-vitro hyperglycemia induced a dose-dependent increase of IL-8 in all age groups while TNF-α was demonstrated to be stimulated by glucose in cord blood samples of preterm infants ≤32 weeks of gestational age and term infants. In contrast, insulin showed no significant effects on pro-inflammatory cytokine production in-vitro.
  
  
  CONCLUSIONS
  Acute hyperglycemia may induce pro-inflammatory cytokine responses in neonatal whole blood in-vitro. These data provide a basis for further in-vitro signal transduction studies and in-vivo investigations about the significance of neonatal glucose homeostasis and its impact on long-term outcome of this susceptible patient cohort.
authors.affiliation: Department of Paediatrics, University Hospital Schleswig-Holstein, Campus Lübeck, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Temming
authors.forename: Birte
authors.initials: B
authors.lastname: Tröger
authors.forename: Susanne
authors.initials: S
authors.lastname: Thonnissen
authors.forename: Paul-Martin
authors.initials: PM
authors.lastname: Holterhus
authors.forename: Christian
authors.initials: C
authors.lastname: Schultz
authors.forename: Christoph
authors.initials: C
authors.lastname: Härtel
mesh_terms: D016207:Cytokines / Q000097:blood; D005312:Fetal Blood / Q000737:chemistry / Q000276:immunology; D005865:Gestational Age; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology*; D007231:Infant, Newborn; D007234:Infant, Premature / Q000097:blood* / Q000276:immunology*; D007235:Infant, Premature, Diseases / Q000097:blood / Q000276:immunology; D007328:Insulin / Q000008:administration & dosage; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008954:Models, Biological; D018805:Sepsis / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D007328:Insulin; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose