Inflammation occurs rapidly in response to acute brain insults such as
stroke, haemorrhage or
trauma, and can be sustained for long periods of time, for example in Alzheimer's or Parkinson's diseases and
multiple sclerosis. Experimental evidence indicates that
inflammation plays a major role in neurodegeneration under these conditions, and that the
cytokine IL-1 (interleukin-1) is a pivotal mediator.
IL-1 is expressed rapidly in response to neuronal injury, predominantly by microglia, and elevated levels of endogenous or exogenous
IL-1 markedly exacerbate injury. The naturally occurring
IL-1RA (
IL-1 receptor antagonist) markedly inhibits ischaemic, excitotoxic and
traumatic brain injury in rodents, and has shown promise in a Phase II clinical trial in
stroke patients. The mechanisms of
IL-1 expression, release and action in neurodegeneration are not fully elucidated and appear multiple. Systemic
IL-1 markedly enhances ischaemic
brain injury via release of neutrophils into circulation, neutrophil adhesion to injured cerebrovasculature and CNS (central nervous system) invasion, and cell death via activation of
matrix metalloproteinase-9.
IL-1 also influences the release of toxins from glial and endothelial cells. Neuronal responses to
excitotoxins and physiological factors may have an impact on neuronal survival.
IL-1RA, delivered peripherally, can enter the CNS in animals and humans and has no adverse effects in
stroke or subarachnoid haemorrhage patients, but shows potential benefit in
acute stroke patients.