Suppression of oxidative neuronal damage after transient middle cerebral artery occlusion in mice lacking interleukin-1.

Interleukin-1 (IL-1) contributes to ischemic neurodegeneration. However, the mechanisms regulating action of IL-1 are still poorly understood. In order to clear this central issue, mice that were gene deficient in IL-1alpha and beta (IL-1 KO) and wild-type mice were subjected to 1-h transient middle cerebral artery occlusion (tMCAO). Expression levels of IL-1beta and IL-1 receptor I (IL-1RI) were then examined. Generation of peroxynitrite and the expression of mRNAs for nitric oxide synthase (NOS) subtypes were also determined. Immunostaining for IL-1beta was increased from 6 h and peaked at 24 h after tMCAO in the microglia and macrophage. The immunoreactivities of IL-1RI were increased progressively in the microvasculature and neuron-like cells of the ipsilateral hemisphere. Infarct volumes were significantly lower in IL-1 KO mice compared with wild-type mice 48 h after tMCAO (P<0.01). The immunoreactivities of 3-nitro-L-tyrosine were determined in the neurons and microvasculature 24 h after tMCAO and were significantly decreased in the IL-1 KO mice compared to wild-type mice. In addition, expression levels of NOS mRNA in IL-1 KO mice were lower than that measured in wild-type mice. These results indicate that IL-1 is up-regulated and may play a role in neurodegeneration by peroxynitrite production during ischemia.