Interleukin-1 in Cerebral Ischemia
During the past several years, it has become increasingly apparent that interleukin-1 (IL-1), particularly IL-1β plays an important role in brain injury during ischemia. Studies from various laboratories have shown that IL-1β mRNA and IL-1β protein are synthesized early in ischemia and that the injection of IL-1β into ischemic brain enhances edema formation. The most direct evidence that IL-1β contributes to ischemic injury, however, is the demonstration that infarct volume in focal ischemia is reduced following intraventricular injection of an endogenous interleukin-1 receptor antagonist (IL-1ra), or after IL-lra is overexpressed in brain using an adenoviral vector to transfer IL-Ira cDNA to brain cells. Ischemic injury is also reduced in mice that fail to produce IL-1β because of an abnormal interleukin-1β converting enzyme gene (ICE knockout mice). At the present time, it is unclear how IL-1β causes brain injury, but several possible mechanisms include 1) stimulation of an inflammatory response through the activation of glia or the induction of other cytokines and/or endothelial adhesion molecules and 2) release of free radicals through stimulation of arachidonic acid metabolism and/or nitric oxide synthase activity.
- Keio journal of medicine
Keio journal of medicine 45(3), 230-238, 1996-09-01
The Keio Journal of Medicine