Cytokines and chemokines in meningeal inflammation: biology and clinical implications.

Abstract

The CNS differs from other tissues in the body by the elaboration of a tight blood-brain barrier (BBB), which drastically reduces access of leukocytes and plasma components to the subarachnoid space and brain parenchyma. During infections of the CNS, an inflammatory reaction occurs across the BBB that can affect the subarachnoid space (meningitis), the brain parenchyma (encephalitis), or both (meningoencephalitis). The composition and time course of CNS inflammation vary greatly. Acute bacterial meningitis is characterized by a rapid accumulation of granulocytes in the CSF that evolves within hours. Viral forms of meningitis are associated with moderate numbers of mononuclear WBCs. The extent of cellular inflammation in encephalitis can vary from occasional cells in the parenchyma to extensive perivascular inflammatory cuffs. Inflammation of the CNS is of great clinical relevance for at least two reasons. First, the inflammatory reaction to the invading CNS pathogen, rather than the pathogen itself, appears to be largely responsible for the damage that results from many CNS infections. In bacterial meningitis, evidence of brain damage can progress long after the site of infection has been sterilized by antibiotic therapy. Conversely, CNS inflammation that is induced without microbial pathogens, for example by expressing a chemokine under a brain-specific promotor, can lead to brain damage similar to that seen in infectious encephalitis [1]. Second, CNS inflammation is notably ineffective in eliminating many pathogens. If bacterial meningitis and acute and chronic CNS infections caused by other pathogens (e.g., herpes simplex virus, spirochetes, rabies virus) are not treated adequately, they either progress rapidly to death or establish chronic infections.