Research Topic

IL-1 inhibition

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Interleukin 1 (IL-1) is a crucial mediator of the inflammatory response, playing an important part in the body's natural responses and the development of pathological conditions leading to chronic inflammation.

There are two distinct forms of IL-1, IL-1α and IL-1β, which are both ...

Interleukin 1 (IL-1) is a crucial mediator of the inflammatory response, playing an important part in the body's natural responses and the development of pathological conditions leading to chronic inflammation.

There are two distinct forms of IL-1, IL-1α and IL-1β, which are both synthesized as precursor peptides (pro-forms) and are cleaved to generate mature IL-1α and IL-1β. While pro-IL-1β is biologically inactive, both pro- and mature IL-1α can bind to their receptors and induce cellular responses.

IL-1 production is tightly controlled at several levels. These include the regulation of gene transcription, mRNA turnover, translation and secretion, and, in the case of IL-1ß, the regulation of inflammasome activation.

Several naturally occurring inhibitors, such as IL-1 receptor antagonist, IL-1 receptor type II, and other soluble receptors, importantly regulate the effects of IL-1α and IL-1ß.

Specific IL-1–targeting therapies have produced, in the last decades, dramatic beneficial effects in a wide spectrum of IL-1 driven diseases.

There are presently three approved therapies for blocking IL-1 activity. Anakinra is a recombinant form of the naturally occurring IL-1 receptor antagonist, which binds to the IL-1 receptor and prevents the binding of IL-1β as well as IL-1α. Rilonacept is a soluble decoy receptor fusion protein that binds IL-1ß and IL-1α preventing activation of cell surface receptors. Canakinumab is a human monoclonal antibody that neutralizes only IL-1β.

IL-1 inhibitors have been initially tested in rheumatoid arthritis, with only modest effects. By contrast, the use of IL-1 antagonists has shown to have beneficial effects in patients with autoinflammatory conditions associated with excessive IL-1 production. The implication of IL-1 in the inflammatory process triggered by pathogenic crystals has provided the rationale for the use of IL-1 inhibitors in crystal-induced arthritis. IL-1 blocking has shown to be effective also in type 2 diabetes through ß cell function restoration, in heart failure, in the indolent stages of multiple myeloma, and, more recently, in some types of cancers associated with IL-1α-mediated inflammation.

In this research topic we focus on recent research exploring of IL-1-targeting therapies.


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