Interleukin 36 receptor antagonist

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Interleukin 36 receptor antagonist (IL-36RA) is a member of the interleukin-36 family of cytokines. It was previously named Interleukin-1 family member 5 (IL1F5).[1][2][3][4]

The protein is known to inhibit the effects of Interleukin-36 cytokines (IL-36α, IL-36β and IL-36γ) via competing with their receptor IL-36R/IL1RL2 and thereby inhibiting their proinflammatory effects.[5]

Roles in disease

Mutations in the IL-36RN gene resulting in a decrease or production of defective IL-36RA protein have been shown to cause inflammatory skin diseases including generalised pustular psoriasis, acrodermatitis continua suppurativa Hallopeau (ACH) and acute generalized exanthematous pustulosis (AGEP).[6]


  1. Smith DE, Renshaw BR, Ketchem RR, Kubin M, Garka KE, Sims JE (Feb 2000). "Four new members expand the interleukin-1 superfamily". J Biol Chem. 275 (2): 1169–75. doi:10.1074/jbc.275.2.1169. PMID 10625660.
  2. Mulero JJ, Pace AM, Nelken ST, Loeb DB, Correa TR, Drmanac R, Ford JE (Nov 1999). "IL1HY1: A novel interleukin-1 receptor antagonist gene". Biochem Biophys Res Commun. 263 (3): 702–6. doi:10.1006/bbrc.1999.1440. PMID 10512743.
  3. Sims JE, Nicklin MJ, Bazan JF, Barton JL, Busfield SJ, Ford JE, Kastelein RA, Kumar S, Lin H, Mulero JJ, Pan J, Pan Y, Smith DE, Young PR (Sep 2001). "A new nomenclature for IL-1-family genes". Trends Immunol. 22 (10): 536–7. doi:10.1016/S1471-4906(01)02040-3. PMID 11574262.
  4. "Entrez Gene: IL36RN interleukin 36 receptor antagonist".
  5. Towne, JE; Garka, KE; Renshaw, BR; Virca, GD; Sims, JE (2 April 2004). "Interleukin (IL)-1F6, IL-1F8, and IL-1F9 signal through IL-1Rrp2 and IL-1RAcP to activate the pathway leading to NF-kappaB and MAPKs". The Journal of Biological Chemistry. 279 (14): 13677–88. doi:10.1074/jbc.M400117200. PMID 14734551.
  6. Navarini, AA; Valeyrie-Allanore, L; Setta-Kaffetzi, N; Barker, JN; Capon, F; Creamer, D; Roujeau, JC; Sekula, P; Simpson, MA; Trembath, RC; Mockenhaupt, M; Smith, CH (July 2013). "Rare variations in IL36RN in severe adverse drug reactions manifesting as acute generalized exanthematous pustulosis". The Journal of Investigative Dermatology. 133 (7): 1904–7. doi:10.1038/jid.2013.44. PMID 23358093.

[1]==Further reading==

  1. Macleod, T; Doble, R; McGonagle, D; Wasson, CW; Alase, A; Stacey, M; Wittmann, M (22 April 2016). "Neutrophil Elastase-mediated proteolysis activates the anti-inflammatory cytokine IL-36 Receptor antagonist". Scientific Reports. 6: 24880. doi:10.1038/srep24880. PMC 4840362. PMID 27101808.