Reactome | IL1R1 binds IL1R1 inhibitors

IL1R1 binds IL1R1 inhibitors

Stable Identifier

R-HSA-9681763

Type

Reaction [binding]

Species

Homo sapiens

Compartment

extracellular region, plasma membrane

ReviewStatus

5/5

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The IL1 family includes two agonists, IL1α and IL1β, and a naturally occurring receptor antagonist, IL1Ra. IL1Ra is produced locally in various tissues in response to infection or inflammation (Arend & Gabay 2000). Anakinra (Kineret) is a recombinant form of IL1Ra that competitively inhibit the local inflammatory effects of IL1 (Seckinger et al. 1990) and is approved for the treatment of rheumatoid arthritis (RA) in combination with methotrexate (Drevlow et al. 1996, Cohen et al. 2002, Fleischmann et al. 2003). Isunakinra (EBI 005) is a fusion protein containing domains from IL1β and the IL1 receptor antagonist (IL1Ra or anakinra) developed as a topical therapy for dry eye disease (Goldstein et al. 2017). It blocks IL1R1 signalling with higher affinity than anakinra (Kovalchin et al. 2018). These IL1R1 inhibitors may be investigated for their role in blocking inflammatory cytokines produced in the "cytokine storm syndrome" caused by COVID-19 (Cron & Chatham 2020).

Literature References

PubMed ID	Title	Journal	Year
27466718	Multicenter Study of a Novel Topical Interleukin-1 Receptor Inhibitor, Isunakinra, in Subjects With Moderate to Severe Dry Eye Disease Sheppard, J, Martel, JR, Korenfeld, M, Durham, TA, Tauber, J, Furfine, E, Rubin, J, Goldberg, DF, Abrams, M, Sall, K, Agahigian, J, Goldstein, MH	Eye Contact Lens	2017
11094434	Physiologic role of interleukin-1 receptor antagonist Arend, WP, Gabay, C	Arthritis Res.	2000
2147937	Natural and recombinant human IL-1 receptor antagonists block the effects of IL-1 on bone resorption and prostaglandin production Seckinger, P, Thompson, RC, Raisz, LG, Dayer, JM, Alander, C, Klein-Nulend, J	J. Immunol.	1990