AGE-RELATED EFFECTS OF INTERLEUKIN-1-BETA ON POLYMORPHONUCLEAR NEUTROPHIL-DEPENDENT INCREASES IN BLOOD-BRAIN-BARRIER PERMEABILITY IN RATS

In adult rats, 50 000 units of recombinant interleukin-1 beta (IL-1 be ta) injected into the brain parenchyma produced an intense meningitis and disruption of the blood-CSF barrier by 4 h. No increase in vascula r permeability to horseradish peroxidase or leukocyte recruitment was observed at the site of injection. By contrast, in juvenile mts, 100 u nits of IL-1 beta injected into the striatum gave rise to a large incr ease in blood-brain barrier permeability and recruitment of polymorpho nuclear 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 a n increase in permeability of vessels to serum proteins in the meninge s, but no increase in vascular permeability was observed at the inject ion site. The IL-1 beta-induced increases in vessel permeability in th e meninges, parenchyma, and choroid plexus were polymorphonuclear neut rophil dependent, since leukocyte depletion by irradiation or polymorp honuclear 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 o f both adults and juvenile animals failed to induce an increase in blo od-brain barrier permeability or polymorphonuclear neutrophil recruitm ent, but did give rise to a mild meningitis. These findings demonstrat e clear differences in the responsiveness of different CNS compartment s to IL-1 beta. Furthermore, while tumour necrosis factor-alpha and IL -1 beta might have been expected to exhibit similar proinflammatory ef fects in the CNS, this is not the case. We also show, for the first ti me, that age has a significant effect on the response to a cytokine. T he '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 C NS.