Perspectives Series: Cytokines and The Brain The Role of Interleukin 1 in Acute Neurodegeneration and Stroke: Pathophysiological and Therapeutic Implications

The last 5 yr have witnessed significant changes in research di-rection and new discoveries about the mechanisms of neurodegeneration. Earlier studies on neuronal death focused on neurons, neuronal pathways, and neurotransmitters. Now similar interest is directed toward glia and vascular cells, peptides, and inflammatory processes in the brain. This research has already revealed several potential therapeutic targets for the treatment of acute brain damage such as stroke and brain injury. The brain fails to exhibit a classical “inflammatory response,” generally characterized by early invasion of macrophages and leukocytes. Nevertheless, the brain can exhibit many of the hallmarks of inflammation when subjected to ischemia, injury, or infection. Such responses include edema, activation of resi-dent phagocytic cells (microglia), invasion of circulating immune cells, and activation or induction of numerous inflammatory molecules including cyclooxygenase products, kinins, complement, acute phase proteins, and proinflammatory cytokines. Of the cytokines, we have identified IL-1 as a mediator of diverse forms of acute neurodegeneration. IL-1 has also been implicated in chronic neurological conditions.