Interleukin-1 receptor axis (IL-1/IL-1R axis)

The Interleukin-1 (IL-1) receptor axis is a fundamental signaling pathway in the innate immune system, primarily responsible for mediating inflammatory responses [1][2]. This axis is triggered by the binding of the proinflammatory cytokines IL-1α or IL-1β to the Interleukin-1 receptor type 1 (IL-1R1), which then associates with the IL-1 receptor accessory protein (IL-1RAcP) to initiate downstream signaling [2][5]. These signals activate transcription factors like NF-κB, leading to the production of various inflammatory mediators, including IL-6 and cyclooxygenase-2 [1]. Dysregulation of the IL-1 axis is a hallmark of many autoinflammatory and chronic inflammatory conditions, such as Cryopyrin-Associated Periodic Syndromes (CAPS), rheumatoid arthritis, and gout [1][4]. Consequently, the axis has become a major therapeutic target, with several approved drugs designed to inhibit its activity [4]. These include anakinra, a recombinant version of the naturally occurring IL-1 receptor antagonist; canakinumab, a monoclonal antibody targeting IL-1β; and rilonacept, a dimeric fusion protein that acts as a decoy receptor [1][4]. Modulation of this pathway is also being explored for its potential benefits in treating cardiovascular diseases, such as recurrent pericarditis and atherosclerosis [3]. By blocking this axis, clinicians can effectively reduce systemic inflammation and manage symptoms in patients with refractory autoinflammatory diseases [1][4].

Other names

IL-1 signaling pathwayIL-1 systemInterleukin-1/Interleukin-1 receptor systemIL-1/IL-1R axis

Drugs targeting the IL-1 receptor axis function by preventing the binding of IL-1 ligands to the IL-1 receptor. This is achieved through competitive antagonism of the receptor (e.g., anakinra), neutralization of circulating cytokines (e.g., canakinumab for IL-1β or bermekimab for IL-1α), or the use of soluble decoy receptors that trap the cytokines before they reach the cell surface (e.g., rilonacept) [1][4].