The CNS inflammatory response is regulated by hepatic
chemokine synthesis, which promotes
leukocytosis and facilitates leukocyte recruitment to the site of injury. To understand the role of the individual cell populations in the liver during the hepatic response to
acute brain injury, we selectively depleted Kupffer cells (KC), using
clodronate-filled
liposomes, and assessed the inflammatory response following a microinjection of IL-1beta into the rat brain or after a compression injury in the spinal cord. We show by immunohistochemistry that KC depletion reduces neutrophil infiltration into the IL-1beta-injected brain by 70% and by 50% into the
contusion-injured spinal cord. qRT-PCR analysis of hepatic
chemokine mRNA expression showed that
chemokine expression in the liver after
brain injury is not restricted to a single cell population. In non-depleted rats, CXCL-10, IL-1beta, CCL-2, and
MIP-1alpha mRNAs were increased up to sixfold more than in KC depleted rats. However, CXCL-1 and
MIP-1beta were not significantly affected by KC depletion. The reduction in
chemokine mRNA expression by the liver was not associated with decreased neutrophil mobilisation as might have been expected. These findings suggest that in response to CNS injury, KC mediated mechanisms are responsible for increasing neutrophil entry to the site of CNS injury, but that neutrophil mobilisation is dependent on other non-KC mediated events. However, the suppression of KC activity may prevent secondary damage after
acute brain injury.