Inflammatory mediators and neonatal brain damage.

Inflammatory mediators are multifunctional cytokines that play important roles both in normal central nervous system (CNS) development and in the response of the brain to diverse forms of injury. Interleukin (IL)-1beta, tumor necrosis factor-alpha and IL-6 are among the best-characterized early-response cytokines. Recent data suggest that they may be synthesized and secreted by several CNS cell types, including microglia, astrocytes and neurons. Biological effects of these cytokines that could influence the progression of injury in the brain include stimulating the synthesis of other cytokines and neuronal injury mediators such as nitric oxide synthase, inducing leukocyte infiltration and the expression of adhesion molecules, influencing glial gene expression and damaging oligodendrocytes. In the immature brain, proinflammatory cytokines might lead to white matter damage during prenatal intrauterine infection and contribute to progressive neuronal damage in acute brain injury evoked by cerebral hypoxia-ischemia. Interrupting the proinflammatory cascade might limit the extent of irreversible injury.