Brain, Vol 120, Issue 3 435-444, Copyright © 1997 by Oxford University Press
DC Anthony, SJ Bolton, S Fearn and VH Perry
In adult rats, 50,000 units of recombinant interleukin-1 beta (IL-1 beta)
injected into the brain parenchyma produced an intense meningitis and
disruption of the blood-CSF barrier by 4 h. No increase in vascular
permeability to horseradish peroxidase or leukocyte recruitment was
observed at the site of injection. By contrast, in juvenile rats, 100 units
of IL-1 beta injected into the striatum gave rise to a large increase in
blood-brain barrier permeability and recruitment of polymorphonuclear
neutrophils into the tissue around the injection site by 4 h. This effect
was also accompanied by a marked meningitis. The injection of 100 units of
IL-1 beta into neonatal (2-h-old) rats gave rise to an increase in
permeability of vessels to serum proteins in the meninges, but no increase
in vascular permeability was observed at the injection site. The IL-1
beta-induced increases in vessel permeability in the meninges, parenchyma,
and choroid plexus were polymorphonuclear neutrophil dependent, since
leukocyte depletion by irradiation or polymorphonuclear neutrophil
anti-serum pre-treatment eliminated the response in the juvenile animals
and in the adults. Seventy-five thousand units of murine tumour necrosis
factor-alpha injected into the parenchyma of both adults and juvenile
animals failed to induce an increase in blood-brain barrier permeability or
polymorphonuclear neutrophil recruitment, but did give rise to a mild
meningitis. These findings demonstrate clear differences in the
responsiveness of different CNS compartments to IL-1 beta. Furthermore,
while tumour necrosis factor-alpha and IL-1 beta might have been expected
to exhibit similar proinflammatory effects in the CNS, this is not the
case. We also show, for the first time, that age has a significant effect
on the response to a cytokine. The "window of susceptibility' to an
inflammatory stimulus in juvenile rats, if paralleled in humans, may be a
major factor in the increased susceptibility of children to trauma or to
infectious insults to the CNS.
ARTICLES
Age-related effects of interleukin-1 beta on polymorphonuclear neutrophil-dependent increases in blood-brain barrier permeability in rats
Department of Pharmacology, University of Oxford, UK.
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