Cytokines and ischemic brain damage

Cytokines are polypeptides that include the families of interleukins (IL-1), tumor necrosis factors (TNF), interferons and growth factors with diverse actions on development, inflammation, tissue injury and repair in almost all cells in the body. The past decade has witnessed increasing interest in the functions and importance of cytokines in central nervous system biology and pathology.

Most cytokines are produced at low levels in healthy adult brains, but many are upregulated rapidly in response to injury, infection or inflammation in the brain including cerebral ischemia. The influence of cytokines on ischemic brain damage appears to be diverse and complex. While several cytokines have clearly identified neurotrophic or neuroprotective effects (e.g., IL-6, insulin-like growth factor (IGF), nerve growth factor (NGF), fibroblast growth factor (FGF), transforming growth factor-β (TGF-β)), others have been implicated as mediators of cell damage (most notably IL-1), while for some (such as TNF-α) both neuroprotective and neurotoxic effects have been identified. This review will focus on the actions of IL-1 on ischemic brain damage and recent findings about its mechanisms of action.

IL-1 expression in stroke

IL-1, IL-1α and IL-1β, and IL-1 receptor antagonist (IL-1ra) are all rapidly produced in response to experimental stroke and excitotoxic and traumatic brain injury in rodents. Temporal studies on expression indicate that IL-1β is produced most extensively and rapidly, initially by microglia and meningeal macrophages and later by astrocytes and invading immune cells.