Cytokine response in cerebrospinal fluid from preterm infants with posthaemorrhagic ventricular dilatation.
OBJECTIVE
Posthaemorrhagic ventricular dilatation (PHVD) is closely associated with white matter damage and neurological disability in the preterm infant. Proinflammatory cytokines have been implicated in the pathogenesis of white matter injury and subsequent cerebral palsy. The aim of this study was to determine the levels of proinflammatory cytokines in cerebrospinal fluid (CSF) from preterm infants with PHVD and to correlate the levels to white matter damage and neurodevelopmental outcome.


METHODS
CSF samples were obtained from 24 preterm infants with expanding PHVD and 19 preterm infants with normal ultrasound. Tumour necrosis factor-alphaa (TNF-alpha ), interleukin-1beta (IL-1beta), interleukin-8 (IL-8) and interferon-gamma (IFN-gamma) in CSF were measured by enzyme-linked immunosorbent assay, and IL-6 was measured by bioassay.


RESULTS
The concentrations of TNF-alpha, IL-1beta, IL-6 and IL-8 were significantly elevated in CSF from infants with PHVD. TNF-alpha was detected in 43% of PHVD infants and 11% of controls (p = 0.04). IL-1beta was detected in 67% of PHVD infants and 0% of controls (p < 0.0001). The concentrations of IL-6 were 368 (145-460) pg ml(-1) in the PHVD group and 30 (25-41) pg ml(-1) in the control group (p < 0.0001), and those of IL-8 were 3000 (1620-3400) pg ml(-1) in the PHVD group and 35 (0-230) pg ml(-1) in the control group (p < 0.0001). Cytokine concentrations did not correlate with white matter lesions on ultrasound, shunt dependence or neurological outcome within the PHVD group.


CONCLUSIONS
There was an intense and prolonged inflammatory reaction in CSF from preterm infants with PHVD and a high risk for subsequent white matter injury and permanent neurological impairment.
Sävman
K
K
Perinatal Center, Department of Pediatrics, Göteborg University, The Queen Silvia Children's Hospital, SE-416 85 Göteborg, Sweden. karin.savman@pediat.gu.se
Blennow
M
M
Hagberg
H
H
Tarkowski
E
E
Thoresen
M
M
Whitelaw
A
A
D002543:Cerebral Hemorrhage / Q000134:cerebrospinal fluid* / Q000000981:diagnostic imaging / Q000473:pathology; D002552:Cerebral Ventricles / Q000000981:diagnostic imaging / Q000473:pathology*; D016207:Cytokines / Q000134:cerebrospinal fluid*; D004108:Dilatation, Pathologic; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature / Q000134:cerebrospinal fluid*; D007371:Interferon-gamma / Q000134:cerebrospinal fluid; D007375:Interleukin-1 / Q000134:cerebrospinal fluid; D015850:Interleukin-6 / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000134:cerebrospinal fluid; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid; D014463:Ultrasonography
D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma