Research

Neonatal high pressure hydrocephalus is associated with elevation of pro-inflammatory cytokines IL-18 and IFNγ in cerebrospinal fluid

Deborah A Sival¹ , Ursula Felderhoff-Müser² , Thomas Schmitz³ , Eelco W Hoving⁴ , Carlo Schaller⁵ and Axel Heep⁶

¹  Department of Pediatrics, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700RB Groningen, The Netherlands

²  Department of Kinderheilkunde Zentrum für Kinder- und Jugendmedizin, Universitätsklinikum Essen, Hufelandstrasse 55, D-45122 Essen, Germany

³  Department of Neonatology, Campus Virchow Klinikum, Charité – Universitätsmedizin Berlin, 13353 Berlin, Germany

⁴  Department of Neurosurgery, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9700RB Groningen, The Netherlands

⁵  Department of Neurosurgery, University of Bonn Medical Center, Sigmund-Freud-Str 25, 53127 Bonn, Germany

⁶  Department of Neonatology, University of Bonn, Adenauerallee 119, 53113, Bonn, Germany

author email corresponding author email

Cerebrospinal Fluid Research 2008, 5:21doi:10.1186/1743-8454-5-21

Published:	31 December 2008

Abstract

Background

In human neonatal high pressure hydrocephalus (HPHC), diffuse white matter injury and gliosis predispose to poor neuro-developmental outcome. The underlying mechanism for diffuse white matter damage in neonatal HPHC is still unclear. Analogous to inflammatory white matter damage after neonatal hypoxemia/ischemia, we hypothesized that pro-inflammatory cytokines could be involved in neonatal HPHC. If so, early anti-inflammatory therapy could ameliorate white matter damage in HPHC, before irreversible apoptosis has occurred. In HPHC and control neonates, we therefore aimed to compare cerebrospinal fluid (CSF) concentrations of IL18, IFNγ and sFasL (interleukin 18, interferon gamma and apoptosis marker soluble-Fas ligand, respectively).

Methods

In neonatal HPHC (n = 30) and controls (n = 15), we compared CSF concentrations of IL18, IFNγ and sFasL using sandwich ELISA. HPHC was grouped according to etiology: spina bifida aperta (n = 20), aqueduct stenosis (n = 4), and fetal intra-cerebral haemorrhage (n = 6). Neonatal control CSF was derived from otherwise healthy neonates (n = 15), who underwent lumbar puncture for exclusion of meningitis.

Results

In all three HPHC groups, CSF IL18 concentrations were significantly higher than control values, and the fetal intracranial haemorrhage group was significantly higher than SBA group. Similarly, in all HPHC groups CSF-IFNγ concentrations significantly exceeded the control group. In both HPHC and control neonates, CSF FasL concentrations remained within the range of reference values.

Conclusion

Independent of the pathogenesis, neonatal HPHC is associated with the activation of the pro-inflammatory cytokines (IL-18 and IFNγ) in the CSF, whereas CSF apoptosis biomarkers (sFasL) were unchanged. This suggests that anti-inflammatory treatment (in addition to shunting) could be helpful to preserve cerebral white matter.