There is a robust and transient innate immune response in the brain during
endotoxemia, which is associated with a cascade of
NF-kappaB signaling events and transcriptional activation of genes that encode
TNF-alpha and the
LPS receptor CD14. The present study investigated whether circulating LPS has the ability to modulate the cerebral innate immune response caused by an intrastriatal (IS) injection of the
endotoxin. We also tested the possibility that CD14 plays a role in these effects and male rats received an intracerebroventricular injection with an anti-CD14 before the IS LPS administration. The single LPS bolus into the striatum caused a strong and time-dependent transcriptional activation of
TNF-alpha,
IkappaBalpha, CD14, and
monocyte chemoattractant protein-1 mRNA in microglial cells ipsilateral to the site of injection. Surprisingly, this wave of induced transcripts was essentially abolished by the systemic
endotoxin pretreatment. Such anti-inflammatory properties of circulating LPS are mediated via plasma
corticosterone, because exogenous
corticoids mimicked while
glucocorticoid receptor antagonist
RU486 prevented the effects of systemic
endotoxin challenge. Of interest is the partial involvement of CD14 in LPS-induced
neuroinflammation; the anti-CD14 significantly abolished the microglial activity at day 3, but not at times earlier. The inflammatory response provoked by an acute intraparenchymal LPS bolus was not associated with convincing neurodegenerative processes. These data provide compelling evidence that systemic
inflammation, through the increase in circulating
glucocorticoids, has the ability to prevent the cerebral innate immune reaction triggered by an IS
endotoxin injection. This study also further consolidates the existence of such system in the brain, which is finely regulated and its transient activation is not harmful for the neuronal elements.