Interleukin-1 signaling pathway components (IL-1 pathway)

The Interleukin-1 (IL-1) signaling pathway is a central mediator of the innate immune response and chronic inflammation (Dinarello, 2011). It is primarily activated by the binding of ligands IL-1α or IL-1β to the Interleukin-1 receptor type 1 (IL-1R1), which then recruits the Interleukin-1 receptor accessory protein (IL-1RAcP) to form a functional signaling complex (Weber et al., 2010; Boraschi & Tagliabue, 2013). This assembly triggers an intracellular cascade involving the adaptor protein MyD88 and Interleukin-1 receptor-associated kinases (IRAKs), leading to the activation of NF-κB and MAPK pathways and the subsequent expression of various inflammatory genes (Weber et al., 2010). Dysregulation of IL-1 signaling is a key driver in numerous pathological conditions, including autoinflammatory syndromes like CAPS, chronic inflammatory diseases such as rheumatoid arthritis and gout, and cardiovascular diseases like atherosclerosis (Dinarello, 2011; Ridker et al., 2017). Therapeutic interventions targeting this pathway include the IL-1 receptor antagonist anakinra, the anti-IL-1β monoclonal antibody canakinumab, and the IL-1 trap rilonacept, all of which aim to mitigate excessive inflammation by preventing receptor activation (Dinarello, 2011). These agents are effective in reducing systemic inflammation, as evidenced by significant decreases in biomarkers like C-reactive protein (CRP) (Ridker et al., 2017). However, therapeutic inhibition of IL-1 signaling is associated with an increased risk of serious infections due to its role in host defense (Anakinra Prescribing Information). Ongoing research continues to explore the role of specific pathway components, such as IL-1α versus IL-1β, in distinct disease contexts to refine therapeutic targeting (Dinarello, 2011).

Other names

IL-1 familyIL-1 systemInterleukin-1 signalingIL-1/IL-1R signaling pathway

Inhibition of IL-1 signaling through various modalities, including competitive antagonism of the IL-1 receptor (anakinra), neutralization of the IL-1β ligand (canakinumab), or sequestration of both IL-1α and IL-1β using a soluble decoy receptor (rilonacept) (Dinarello, 2011; FDA).