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 impli cated in the cause of PVL. Methods: The authors investigated the in situ ex pression of proinflammatory cytokines (interleukin-lp and -6, tumor necrosi s factor or [TNF alpha]), adhesion molecules (intercellular adhesion molecu le-1, vascular cell adhesion molecule-1) and inflammatory cell markers (CD6 8, leukocyte common antigen, human leukocyte antigen II) in 19 neonatal bra ins with PVL. The authors compared the findings with matched non-PVL brains . Results: The inflammatory reaction detected at the early stage of PVL ext ends until the latest phase of cystic cavitation, though at an attenuated l evel. There is high expression of TNF alpha and to a lesser extent interleu kin-l beta; interleukin-6 remains undetectable. Cytokine immunoreactivity i s detected in PVL cases both with and without infection. However, cytokine production was higher with infection. A different pattern of cytokine expre ssion was observed in anoxic brains without PVL: TNF alpha immunoreactivity was significantly lower than the PVL group. Conclusions: An immune-mediate d inflammatory process may play a role in PVL. TNF alpha, a myelinotoxic fa ctor, may be the major mediator.