title: Circulating interferon-gamma and white matter brain damage in preterm infants.
abstract: The fetal inflammatory response has been suggested as causal in neonatal morbidity. Serial levels of circulating cytokines were evaluated in 74 infants with a mean gestational age (GA) of 27.1 wk. Pro-inflammatory [tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), IL-1 beta, IL-2, IL-6, IL-8, IL-12] [corrected] and modulatory (IL-4, IL-10) cytokines were analyzed from cord blood, and at 6, 24 [corrected] and 72 h postnatal age. Measure of cytokine burden over time was assessed by calculating the area under curve (AUC) for analyzed levels (0-72 h). Premature rupture of membranes (PROM) was associated with higher levels of IL-2 at birth and at 6 h, of IFN-gamma at 6 and 24 h postnatal age and of TNF-alpha at 6 and 24 h. Levels of IFN-gamma at 6, 24, and 72 h were increased in infants developing white matter brain damage (WMD) compared with those without WMD. Infants with arterial hypotension requiring dopamine treatment had an increase in IL-6 with a peak at 6 h of age. Severe intraventricular hemorrhage (IVH) was associated with increase in AUC [(IL-6) and (IL-8), odds ratio (OR) 2.8 and 13.2 respectively], whereas white matter brain damage (WMD) [corrected] was associated with increase in AUC (IFN-gamma; OR, 26.0) [corrected] A fetal immune response with increased postnatal levels of IFN-gamma was associated with development of WMD. PROM was associated with a T-helper 1 cytokine response with increased levels of IFN-gamma. Type of inflammatory response appears of importance for subsequent morbidity.
authors.affiliation: Department of Pediatrics, Lund University Hospital, 221 85 Lund, Sweden. ingrid.pupp@skane.se
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hansen-Pupp
authors.forename: Solveig
authors.initials: S
authors.lastname: Harling
authors.forename: Ann-Cathrine
authors.initials: AC
authors.lastname: Berg
authors.forename: Corrado
authors.initials: C
authors.lastname: Cilio
authors.forename: Lena
authors.initials: L
authors.lastname: Hellström-Westas
authors.forename: David
authors.initials: D
authors.lastname: Ley
mesh_terms: D019540:Area Under Curve; D001930:Brain Injuries / Q000097:blood* / Q000000981:diagnostic imaging; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D005322:Premature Rupture of Fetal Membranes; D006801:Humans; D007022:Hypotension / Q000097:blood; D007231:Infant, Newborn; D007234:Infant, Premature; D007371:Interferon-gamma / Q000097:blood*; D008297:Male; D011247:Pregnancy; D014463:Ultrasonography
chemical_list: D016207:Cytokines; D007371:Interferon-gamma