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

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, IFNgamma 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, IFNgamma 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-IFNgamma 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 IFNgamma) 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