The interleukin-1 system: an attractive and viable therapeutic target in neurodegenerative disease.

Abstract

Inflammatory processes in the brain have been implicated in both acute and chronic neurodegenerative disease. One of the most studied inflammatory mediators in this respect is the cytokine interleukin-1 (IL-1), which has diverse actions in the central nervous system and mediates a wide variety of effects, including the host defense responses to local and systemic disease and injury. Both pre-clinical and clinical data suggest a role for IL-1 as a key mediator of cell death in acute neurodegenerative conditions, such as stroke and head injury. IL-1 has also been implicated in a number of chronic diseases, including Parkinson's and Alzheimer's disease, as well as in epilepsy. Constitutive expression of IL-1 is very low in normal brain, but is up-regulated rapidly in response to local or peripheral insults. The mechanisms regulating the expression IL-1 are not well defined, but appear to involve multiple effects on neuronal, glial and endothelial cell function. Therefore, the IL-1 system represents an attractive and intensely competitive therapeutic target.