Inflammatory cytokines in the pathogenesis of periventricular leukomalacia.
BACKGROUND
Periventricular leukomalacia (PVL) affects the developing white matter of neonatal brain. Inflammatory and infectious conditions are implicated in the cause of PVL.


METHODS
The authors investigated the in situ expression of proinflammatory cytokines (interleukin-1beta and -6, tumor necrosis factor alpha [TNFalpha]), adhesion molecules (intercellular adhesion molecule-1, vascular cell adhesion molecule-1) and inflammatory cell markers (CD68, leukocyte common antigen, human leukocyte antigen II) in 19 neonatal brains with PVL. The authors compared the findings with matched non-PVL brains.


RESULTS
The inflammatory reaction detected at the early stage of PVL extends until the latest phase of cystic cavitation, though at an attenuated level. There is high expression of TNFalpha and to a lesser extent interleukin-1beta; interleukin-6 remains undetectable. Cytokine immunoreactivity is detected in PVL cases both with and without infection. However, cytokine production was higher with infection. A different pattern of cytokine expression was observed in anoxic brains without PVL: TNFalpha immunoreactivity was significantly lower than the PVL group.


CONCLUSIONS
An immune-mediated inflammatory process may play a role in PVL. TNFalpha, a myelinotoxic factor, may be the major mediator.
Kadhim
H
H
Service de Neurologie Pédiatrique et Laboratoire de Neurologie du Développement, Cliniques Universitaires Saint Luc, Université Catholique de Louvain, Brussels, Belgium. Hazim.Kadhim@nepe.ucl.ac.be
Tabarki
B
B
Verellen
G
G
De Prez
C
C
Rona
A M
AM
Sébire
G
G
D000954:Antigens, Surface / Q000378:metabolism; D001921:Brain / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D002547:Cerebral Palsy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D004660:Encephalitis / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007969:Leukomalacia, Periventricular / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000954:Antigens, Surface; D016207:Cytokines; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha