Interleukin-1 in the central nervous system: from physiology to pathology

A classification on the basis of time-course effect is proposed to describe the pleiotropic actions of interleukin-1 (IL-1) on the central nervous sys tem (CNS); two main time-frames, minutes-to-days and days-to-years, are dis tinguished The former includes the central aspects of acute-phase response with fever, altered food and rvatcr intake, sleepiness, sickness behaviour and neuroendocrine chang es. Apart from stress response triggered by immune -inflammatory stimuli, the concept that IL-1 mediates other types of stress is also reviewed, showing that the cytokine may have a role in mediating h ypothalmic responses to restrain stress and nociceptive stimuli. The days-t o-years time-frame includes several CNS disorders accompanied by inappropri ate and/or sustainedly elevated IL-beta production: ischaemia, Alzheimer's disease, HIV-related dementia and experimental allergic encephalomyelitis-m ultiple sclerosis. In all cases, IL-beta is not envisioned as an aetiologic al factor, but it contributes significantly to the maintenance of disease s tate. Current and perspective therapeutic approaches involving the modulati on of IL-beta production and effects ale briefly discussed.