Interleukin-1 and neuronal injury

• Published in: Nature reviews. Immunology Vol. 5; no. 8; pp. 629 - 640
• Main Authors: Allan, Stuart M., Tyrrell, Pippa J., Rothwell, Nancy J.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.08.2005; Nature Publishing Group
• Subjects: Alzheimer's disease; Animals; Biological effects; Biomedical and Life Sciences; Biomedicine; Central Nervous System - drug effects; Central Nervous System - pathology; Cytokines; Humans; Immunology; Inflammation; Interleukin-1 - genetics; Interleukin-1 - pharmacology; Interleukin-1 - physiology; Nervous system; Neurodegeneration; Neurodegenerative Diseases - immunology; Neurodegenerative Diseases - pathology; Neurons - drug effects; Neurons - pathology; Proteins; review-article; Signal transduction; Trauma; United Kingdom > UK
• ISSN: 1474-1733; 1474-1741
• DOI: 10.1038/nri1664

Key Points Interleukin-1 (IL-1) is a pro-inflammatory cytokine that mediates a diverse range of effects, in both the immune system and the central nervous system. The tight regulatory control of the actions of IL-1 by several endogenous inhibitory molecules, including a receptor antagonist (IL-1RA), is an indicator of the biological importance of IL-1. There is considerable experimental evidence supporting a role for IL-1 as a crucial mediator of neuronal injury in neurodegenerative disease. This includes both acute conditions, such as stroke and head injury, and chronic disorders, such as Alzheimer's disease and Parkinson's disease. The mechanisms of IL-1 action in neuronal injury are not clearly defined and are the subject of intense research effort. There are discrepancies between in vitro and in vivo findings, and IL-1 seems to exert complex effects by influencing multiple cell types in the brain. Clinical data also support a role for IL-1 in neurodegeneration. Consequently, a Phase IIa clinical trial involving IL-1RA treatment of patients who have suffered a stroke has just been completed. Developing a greater understanding of the mechanisms of IL-1 action in neuronal injury, and developing interventions to target these effects, could lead to more effective treatments for stroke and other types of brain injury in the future. Interleukin-1 is a pro-inflammatory cytokine that has numerous biological effects, including activation of many inflammatory processes (through activation of T cells, for example), induction of expression of acute-phase proteins, an important function in neuroimmune responses and direct effects on the brain itself. There is now extensive evidence to support the direct involvement of interleukin-1 in the neuronal injury that occurs in both acute and chronic neurodegenerative disorders. This article discusses the key evidence of a role for interleukin-1 in acute neurodegeneration — for example, stroke and brain trauma — and provides a rationale for targeting the interleukin-1 system as a therapeutic strategy.