Key Points
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Interleukin-1 (IL-1) is a pro-inflammatory cytokine that plays a role in many acute and chronic human diseases.
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Elevated levels of IL-1, or the naturally occurring receptor antagonist IL-1Ra, can be measured in human samples of tissue or body fluids from patients with rheumatoid arthritis (RA), osteoarthritis, chronic obstructive pulmonary disease, asthma, inflammatory bowel disease and atherosclerosis.
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Blockade of IL-1 binding to the IL-1 receptor has been achieved with biological agents that neutralize IL-1. Anakinra, a recombinant form of IL-1Ra, shows clinical efficacy in RA. Other agents show promise in preclinical models and are safe and well tolerated in Phase I volunteer studies.
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Small-molecule drugs are being developed that interfere with IL-1 signalling production or processing. The most advanced of these is an inhibitor of IL-1-converting enzyme, which has has shown clinical efficacy in RA. Other approaches include targeting the post-translational processing or release of IL-1 and have yielded encouraging results in preclinical studies.
Abstract
The cytokine interleukin-1 (IL-1) is important in many human diseases, and drives a wide range of inflammatory responses in a number of cell types. Biological agents that target IL-1 neutralization have shown efficacy in patients with rheumatoid arthritis. Recently, new classes of compounds that target IL-1 production or processing, or regulatory steps on the IL-1 pathway, are being investigated as new drugs for the management of inflammatory disease. Such compounds will have wide utility in numerous inflammatory conditions.
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Acknowledgements
We thank our colleagues in the Respiratory and Inflammation Research Area and in clinical development within AstraZeneca for their support and stimulating discussion.
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Glossary
- AUTOCRINE
-
The secretion of a substance, such as a cytokine, that stimulates the secretory cell itself.
- PROXIMAL
-
Nearest the point of origin of a biochemical pathway or molecular process, as opposed to distal, which represents a point towards or at the end of a pathway or process.
- ACUTE-PHASE PROTEINS
-
Antibody-proteins or glycoproteins usually found in the plasma whose concentration increases in response to infection or injury.
- PHARMACOKINETICS
-
The rate by which a drug is absorbed, distributed, metabolized and eliminated by the body.
- PEGYLATED
-
Attachment of non-toxic polyethylene (PEG) polymers to drug and protein molecules to alter their properties to improve safety and efficacy.
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Braddock, M., Quinn, A. Targeting IL-1 in inflammatory disease: new opportunities for therapeutic intervention. Nat Rev Drug Discov 3, 330–340 (2004). https://doi.org/10.1038/nrd1342
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DOI: https://doi.org/10.1038/nrd1342
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