Luigi Grimaldi, Italy

A fair percentage of patients affected by chronic infectious (e.g. HIV encephalopathy, tertiary syphilis, subacute sclerosing panencephalitis), autoimmune (e.g. multiple sclerosis, paraneoplastic encephalitis) and systemic connective tissue or vasculitic (e.g. sarcoidosis, systemic lupus erithematosus, Beh?et's disease) neurological disorders recognizes a multi-systemic decline of mental and physical abilities associated with inflammatory phenomena potentially able to cause neuronal impairment and loss. Mediators of these phenomena include immunologically relevant molecules (complement fragments, immunoglobulins, cytokines), toxic substances (NO, proteolytic enzymes), and growth factor inhibitors. More recently, molecules well know for their inflammatory properties have been found to participate to the neurodegenerative processes typical of cerebral amyloidoses [Alzheimer's Disease (AD), Pick's disease, fronto-temporal dementias], Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and the parkinsonism dementia complex of Guam. In AD, for instance, the abnormal deposition of normal component of intra- (tau protein) or extra- (b-amyloid protein) neuronal proteins leading to neuronal cell death and cognitive decline seems to be under the influence of a few critical microglia-derived "pro-inflammatory" cytokines, among which a special role is played by members of the IL-1 family [IL-1?, IL-1?, IL-1? (formerly IL-18), IL-1RA, etc.]. It is not clear whether the effects played by these pleiotropic molecules in the context of diseases such as AD stem from classical inflammatory phenomena or from still unbeknown CNS-specific properties. In any case, the recognition of their contribution to the pathogenesis of neurodegenerative disorders is likely to improve our diagnostic and therapeutic skills as well as indicate additional susceptibility traits and potential target(s) for selective, inflammation-specific immune intervention.