Interleukin-1 and inflammatory degeneration

Inflammatory processes in the brain (and systemically) have been linked to neuron loss in CNS disease and injury, including Alzheimer’s Disease, Parkinson’s Disease, MS, stroke, etc. Inflammation in the brain can lead to increased expression of inflammatory mediators, cytokines being a primary one in the inflammatory response. The cytokine IL-1 has been shown to contribute to neuronal loss and may play an important role in neurodegenerative disease. IL-1 is expressed rapidly by microglia in response to injury, and increases brain injury by neutrophil mobilization and cell apoptosis by MMP-9.
Experimental brain insults, including ischaemia, trauma, inflammatory stimuli, etc, increased the expression of the IL-1 family. Administration of this cytokine causes a major increase in neuron cell death after brain injury. In models of Alzheimer’s in mice, B-amyloid- activated microglia produced IL-1, promoting the production of neurotoxic B-amyloid peptides. Furthermore, rat brains with high expression of IL-1 resulted in demyelinating lesions, similar to MS.
IL-1 is not toxic to pure neurons or when injected into healthy brains. Neurotoxicity typically requires cell contact interactions between astrocytes and neurons. IL-1 up-regulates genes in astrocytes that encode neurotoxic mediators, as well as survival-promoting factors. It also acts on endotheilial cells of the brain to up-reulate the expression of adhesion/chemoattractant substances and promote BBB breakdown, which are factors involved in leukocyte recruitment. There are many other examples in this paper of how IL-1 mediates neuron death, but the major focus should be on how we can modify or control this.
IL-1RA(receptor antagonist) is a major player , providing neuroprotection, that researchers are studying. It has been a success in treatment of rheumatoid arthritis, and has shown promise in the Phase II trial in stroke patients. It inhibits ischaemic, excitotoxic and brain injury in rats. There is still a lot of studying to be done on this but with high hopes. Brain injury creates a therapeutic challenge and it is still unclear whether inflammation promotes CNS diseases or is merely a coincidence. With the increased awareness of many neurodegenerative diseases today, I predict that we will know a lot more in the near future.