Mechanisms of regulation for interleukin-1beta in neurodegenerative disease.

The interleukin-1 family of cytokines are central to the pathology of acute and chronic diseases of the central nervous system. We describe current evidence on the transcriptional and post-transcriptional regulation of interleukin-1beta production, secretion and activity in the brain. Regarding the induction of protein synthesis, the possible involvement of Toll like receptor-4 is discussed including evidence that ischemic brain damage is reduced in Toll like receptor-4 knockout mice. The post-translational involvement of the P2X7-receptor and caspase-1 in the processing and release of active IL-1beta is also considered, as is evidence suggesting a possible extracellular cleavage of pro-IL-1beta by neutrophil derived proteases. We provide some fresh perspectives on how interleukin-1beta may be regulated and how these mechanisms could be targeted in disease.