interleukin 1 receptor antagonist protein


Summary: A ligand that binds to but fails to activate the INTERLEUKIN 1 RECEPTOR. It plays an inhibitory role in the regulation of INFLAMMATION and FEVER. Several isoforms of the protein exist due to multiple ALTERNATIVE SPLICING of its mRNA.

Top Publications

  1. van de Veerdonk F, Netea M, Dinarello C, van der Meer J. Anakinra for the inflammatory complications of chronic granulomatous disease. Neth J Med. 2011;69:95 pubmed
  2. Feingold K, Staprans I, Memon R, Moser A, Shigenaga J, Doerrler W, et al. Endotoxin rapidly induces changes in lipid metabolism that produce hypertriglyceridemia: low doses stimulate hepatic triglyceride production while high doses inhibit clearance. J Lipid Res. 1992;33:1765-76 pubmed
  3. Furst D, Keystone E, Braun J, Breedveld F, Burmester G, De Benedetti F, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2011. Ann Rheum Dis. 2012;71 Suppl 2:i2-45 pubmed publisher
  4. Nadeau Vallée M, Chin P, Belarbi L, Brien M, Pundir S, Berryer M, et al. Antenatal Suppression of IL-1 Protects against Inflammation-Induced Fetal Injury and Improves Neonatal and Developmental Outcomes in Mice. J Immunol. 2017;198:2047-2062 pubmed publisher
    ..10 treatment. The results implicate IL-1 as an important driver of neonatal morbidity in PTB and identify 101.10 as a safe and effective candidate therapeutic. ..
  5. Grayson P, Yazici Y, Merideth M, Sen H, Davis M, Novakovich E, et al. Treatment of mucocutaneous manifestations in Behçet's disease with anakinra: a pilot open-label study. Arthritis Res Ther. 2017;19:69 pubmed publisher NCT01441076 . Registered on 24 September 2011. ..
  6. Zhang D, Zou M, Zhang Y, Fu W, Xu T, Wang J, et al. A novel IL-1RA-PEP fusion protein with enhanced brain penetration ameliorates cerebral ischemia-reperfusion injury by inhibition of oxidative stress and neuroinflammation. Exp Neurol. 2017;297:1-13 pubmed publisher
  7. Duffy H, John G, Lee S, Brosnan C, Spray D. Reciprocal regulation of the junctional proteins claudin-1 and connexin43 by interleukin-1beta in primary human fetal astrocytes. J Neurosci. 2000;20:RC114 pubmed
    ..We suggest that in pathological conditions of the human CNS, elevated IL-1beta expression fundamentally alters astrocyte-to-astrocyte connectivity. ..
  8. Peces R, Afonso S, Peces C, Nevado J, Selgas R. Living kidney transplantation between brothers with unrecognized renal amyloidosis as the first manifestation of familial Mediterranean fever: a case report. BMC Med Genet. 2017;18:97 pubmed publisher
    ..Finally, anakinra could be a safe adjuvant therapy combined with colchicine for patients with familial Mediterranean fever and amyloidosis, including those with successful kidney transplantation. ..
  9. Loddick S, Wong M, Bongiorno P, Gold P, Licinio J, Rothwell N. Endogenous interleukin-1 receptor antagonist is neuroprotective. Biochem Biophys Res Commun. 1997;234:211-5 pubmed
    ..To our knowledge this is the first report of an action of endogenous IL-1ra in the brain. Control of IL-1ra expression or action may therefore provide a useful therapeutic strategy to limit acute neurodegeneration. ..

More Information


  1. Barak V, Acker M, Nisman B, Kalickman I, Abrahamov A, Zimran A, et al. Cytokines in Gaucher's disease. Eur Cytokine Netw. 1999;10:205-10 pubmed
    ..Thus, the elevated IL-1beta, TNF-alpha and IL-6 levels may induce the bone manifestations, the neutrophil chemotaxis and the increased incidence of hyper-gammaglobulinemia present in GD patients. ..
  2. Parisi F, Paglionico A, Varriano V, Ferraccioli G, Gremese E. Refractory adult-onset Still disease complicated by macrophage activation syndrome and acute myocarditis: A case report treated with high doses (8?mg/kg/d) of anakinra. Medicine (Baltimore). 2017;96:e6656 pubmed publisher
    ..In AOSD complicated by life-threatening conditions, probably we need to consider aggressive therapeutic approaches with higher doses of Il-1 receptor blocker to switch off the hyper-inflammation. ..
  3. Chao C, Hu S, Ehrlich L, Peterson P. Interleukin-1 and tumor necrosis factor-alpha synergistically mediate neurotoxicity: involvement of nitric oxide and of N-methyl-D-aspartate receptors. Brain Behav Immun. 1995;9:355-65 pubmed
    ..These in vitro findings suggest that agents which suppress NO production or inhibit NMDA receptors may protect against neuronal damage in cytokine-induced neurodegenerative diseases. ..
  4. Gherardi R, Belec L, Soubrier M, Malapert D, Zuber M, Viard J, et al. Overproduction of proinflammatory cytokines imbalanced by their antagonists in POEMS syndrome. Blood. 1996;87:1458-65 pubmed
  5. Gallentine W, Shinnar S, Hesdorffer D, Epstein L, Nordli D, Lewis D, et al. Plasma cytokines associated with febrile status epilepticus in children: A potential biomarker for acute hippocampal injury. Epilepsia. 2017;58:1102-1111 pubmed publisher
    ..If replicated in another study, the IL-1RA/IL-6 ratio could represent a serologic biomarker that offers rapid identification of patients at risk for ultimately developing mesial temporal lobe epilepsy (MTLE). ..
  6. Romero R, Gomez R, Galasso M, Mazor M, Berry S, Quintero R, et al. The natural interleukin-1 receptor antagonist in the fetal, maternal, and amniotic fluid compartments: the effect of gestational age, fetal gender, and intrauterine infection. Am J Obstet Gynecol. 1994;171:912-21 pubmed
  7. Granowitz E, Porat R, Mier J, Pribble J, Stiles D, Bloedow D, et al. Pharmacokinetics, safety and immunomodulatory effects of human recombinant interleukin-1 receptor antagonist in healthy humans. Cytokine. 1992;4:353-60 pubmed
    ..These data suggest that transient blockade of interleukin 1 receptors is safe and does not significantly affect homeostasis. ..
  8. Nigrovic P. Review: is there a window of opportunity for treatment of systemic juvenile idiopathic arthritis?. Arthritis Rheumatol. 2014;66:1405-13 pubmed publisher
  9. Huffmeier U, Wätzold M, Mohr J, Schön M, Mossner R. Successful therapy with anakinra in a patient with generalized pustular psoriasis carrying IL36RN mutations. Br J Dermatol. 2014;170:202-4 pubmed publisher
  10. Vannier E, Miller L, Dinarello C. Coordinated antiinflammatory effects of interleukin 4: interleukin 4 suppresses interleukin 1 production but up-regulates gene expression and synthesis of interleukin 1 receptor antagonist. Proc Natl Acad Sci U S A. 1992;89:4076-80 pubmed
    ..Because IL-4 favors synthesis of the natural antagonist IL-1ra over synthesis of the agonist IL-1, IL-4 may exert potent antiinflammatory effects on host responses to Gram-negative infections. ..
  11. Kuemmerle Deschner J, Verma D, Endres T, Broderick L, de Jesus A, Hofer F, et al. Clinical and Molecular Phenotypes of Low-Penetrance Variants of NLRP3: Diagnostic and Therapeutic Challenges. Arthritis Rheumatol. 2017;69:2233-2240 pubmed publisher
    ..Patients with low-penetrance NLRP3 variants display a distinct clinical phenotype and an intermediate biologic phenotype, including IL-1β and non-IL-1β-mediated inflammatory pathway activation. ..
  12. Upadhyay K, Park J, Yoon T, Halder P, Kim Y, Metcalfe V, et al. Group B Streptococci Induce Proinflammatory Responses via a Protein Kinase D1-Dependent Pathway. J Immunol. 2017;198:4448-4457 pubmed publisher
  13. Camacho Lovillo M, Méndez Santos A. Successful treatment of idiopathic recurrent pericarditis with interleukin-1 receptor antagonist (Anakinra). Pediatr Cardiol. 2013;34:1293-4 pubmed publisher
  14. Mesa F, Lanza E, García L, Marfil Alvarez R, Magan Fernandez A. Polymorphism IL-1RN rs419598 reduces the susceptibility to generalized periodontitis in a population of European descent. PLoS ONE. 2017;12:e0186366 pubmed publisher
    ..This effect may be mediated by a decreased load of Porphyromona gingivalis, Tannerella forsythia, and Prevotella intermedia. ..
  15. Randow F, Syrbe U, Meisel C, Krausch D, Zuckermann H, Platzer C, et al. Mechanism of endotoxin desensitization: involvement of interleukin 10 and transforming growth factor beta. J Exp Med. 1995;181:1887-92 pubmed
    ..In summary, our data suggests that IL-10 and TGF-beta mediate the phenomenon of LPS tolerance in vitro and perhaps in vivo (septic patients), too. ..
  16. Tian T, Jin M, Dubin K, King S, Hoetzenecker W, Murphy G, et al. IL-1R Type 1-Deficient Mice Demonstrate an Impaired Host Immune Response against Cutaneous Vaccinia Virus Infection. J Immunol. 2017;198:4341-4351 pubmed publisher
    ..These results suggest new therapeutic strategies for treatment of eczema vaccinatum and inform assessment of risks in patients receiving IL-1 blocking Abs for treatment of chronic inflammatory disorders. ..
  17. Herder C, de Las Heras Gala T, Carstensen Kirberg M, Huth C, Zierer A, Wahl S, et al. Circulating Levels of Interleukin 1-Receptor Antagonist and Risk of Cardiovascular Disease: Meta-Analysis of Six Population-Based Cohorts. Arterioscler Thromb Vasc Biol. 2017;37:1222-1227 pubmed publisher
    ..This association may at least partially reflect a response to triggers inducing subclinical inflammation, oxidative stress, and endothelial activation. ..
  18. Vassilopoulos D, Lazaros G, Tsioufis C, Vasileiou P, Stefanadis C, Pectasides D. Successful treatment of adult patients with idiopathic recurrent pericarditis with an interleukin-1 receptor antagonist (anakinra). Int J Cardiol. 2012;160:66-8 pubmed publisher
  19. Zhang J, Sun X, Wang J, Zhang F, Li X, Han J. Association of the IL-1RN variable number of tandem repeat polymorphism and Helicobacter pylori infection: A meta-analysis. PLoS ONE. 2017;12:e0175052 pubmed publisher
    ..e., study samples obtained from hospital inpatients). In conclusion, our study demonstrated that IL-1RN VNTR polymorphism might increase the risk of H. pylori infection, especially in Asians. ..
  20. Cavalli G, Fallanca F, Dinarello C, Dagna L. Treating pulmonary silicosis by blocking interleukin 1. Am J Respir Crit Care Med. 2015;191:596-8 pubmed publisher
  21. Lazaros G, Vasileiou P, Koutsianas C, Antonatou K, Stefanadis C, Pectasides D, et al. Anakinra for the management of resistant idiopathic recurrent pericarditis. Initial experience in 10 adult cases. Ann Rheum Dis. 2014;73:2215-7 pubmed publisher
  22. Muhr P, Renne J, Schaefer V, Werfel T, Wittmann M. Primary human keratinocytes efficiently induce IL-1-dependent IL-17 in CCR6+ T cells. Exp Dermatol. 2010;19:1105-7 pubmed publisher
    ..Importantly, co-culture of keratinocytes with CCR6+ CD4+ T cells that are enriched for Th17 cells resulted in significantly higher IL-17 production compared to co-culture with CD4+ T cells. ..
  23. Valdivieso Ã, Mori C, Clauzure M, Massip Copiz M, Santa Coloma T. CFTR modulates RPS27 gene expression using chloride anion as signaling effector. Arch Biochem Biophys. 2017;633:103-109 pubmed publisher
  24. Hack C, Aarden L, Thijs L. Role of cytokines in sepsis. Adv Immunol. 1997;66:101-95 pubmed
  25. Alves De Souza C, Queiroz Alves De Souza A, Queiroz Alves De Souza M, Dias Leite J, Silva De Morais M, Barem Rabenhorst S. A link between osteomyelitis and IL1RN and IL1B polymorphisms-a study in patients from Northeast Brazil. Acta Orthop. 2017;88:556-561 pubmed publisher
    ..These data may be relevant for new therapeutic strategies for this disease. ..
  26. Ombrello M, Kastner D. Autoinflammation in 2010: expanding clinical spectrum and broadening therapeutic horizons. Nat Rev Rheumatol. 2011;7:82-4 pubmed publisher
  27. Bacconnier L, Jorgensen C, Fabre S. Erosive osteoarthritis of the hand: clinical experience with anakinra. Ann Rheum Dis. 2009;68:1078-9 pubmed publisher
  28. Ottaviani S, Moltó A, Ea H, Neveu S, Gill G, Brunier L, et al. Efficacy of anakinra in gouty arthritis: a retrospective study of 40 cases. Arthritis Res Ther. 2013;15:R123 pubmed
    ..Its long-term use could be limited by infectious complications. ..
  29. Lenormand C, Lipsker D. Efficiency of interleukin-1 blockade in refractory delayed-pressure urticaria. Ann Intern Med. 2012;157:599-600 pubmed publisher
  30. Underwood D, Osborn R, Bochnowicz S, Webb E, Rieman D, Lee J, et al. SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am J Physiol Lung Cell Mol Physiol. 2000;279:L895-902 pubmed
    ..Therefore, SB 239063 demonstrates activity against a range of sequelae commonly associated with COPD and fibrosis, supporting the therapeutic potential of p38 MAPK inhibitors such as SB 239063 in chronic airway disease. ..
  31. Landmann E, Walker U. Pharmacological treatment options for cryopyrin-associated periodic syndromes. Expert Rev Clin Pharmacol. 2017;10:855-864 pubmed publisher
    ..Prospective observational studies are needed to confirm long-term efficacy and sustained benefit. New IL-1ß blockers will likely address unmet clinical needs in other autoinflammatory conditions. ..
  32. Cohen S, Tacke C, Straver B, Meijer N, Kuipers I, Kuijpers T. A child with severe relapsing Kawasaki disease rescued by IL-1 receptor blockade and extracorporeal membrane oxygenation. Ann Rheum Dis. 2012;71:2059-61 pubmed publisher
  33. Lee D, Hahm K. Inflammatory cytokine gene polymorphisms and gastric cancer. J Gastroenterol Hepatol. 2008;23:1470-2 pubmed publisher
  34. Durand M, Troyanov Y, Laflamme P, Grégoire G. Macrophage activation syndrome treated with anakinra. J Rheumatol. 2010;37:879-80 pubmed publisher
  35. van den Brand B, Waterborg C, van den Berg W, van de Loo F. Is the serum amyloid A we use really serum amyloid A? Comment on the article by Connolly et al. Arthritis Rheum. 2013;65:283-4 pubmed publisher
  36. Bertani I, Iori V, Trusel M, Maroso M, Foray C, Mantovani S, et al. Inhibition of IL-1? Signaling Normalizes NMDA-Dependent Neurotransmission and Reduces Seizure Susceptibility in a Mouse Model of Creutzfeldt-Jakob Disease. J Neurosci. 2017;37:10278-10289 pubmed publisher
  37. Gorth D, Mauck R, Chiaro J, Mohanraj B, Hebela N, Dodge G, et al. IL-1ra delivered from poly(lactic-co-glycolic acid) microspheres attenuates IL-1?-mediated degradation of nucleus pulposus in vitro. Arthritis Res Ther. 2012;14:R179 pubmed publisher
    ..Ongoing studies are focusing on testing IL-1ra microspheres in an in vivo model of disc degeneration, as a prelude to clinical translation. ..
  38. Antonios J, Yao Z, Li C, Rao A, Goodman S. Macrophage polarization in response to wear particles in vitro. Cell Mol Immunol. 2013;10:471-82 pubmed publisher
    ..The effects of this polarization were sustained over a 5-day time course. Polarization of M1 macrophages into an M2 phenotype may be a strategy to mitigate wear particle associated periprosthetic osteolysis. ..
  39. Hughes F, Sexton S, Jin H, Govada V, Purves J. Bladder fibrosis during outlet obstruction is triggered through the NLRP3 inflammasome and the production of IL-1?. Am J Physiol Renal Physiol. 2017;313:F603-F610 pubmed publisher
    ..In summary, NLRP3-derived-IL-1? triggers fibrosis during BOO, most likely through an autocrine loop in which IL-1? acts on urothelia to drive collagen production. ..
  40. Record J, Beukelman T, Cron R. Combination therapy of abatacept and anakinra in children with refractory systemic juvenile idiopathic arthritis: a retrospective case series. J Rheumatol. 2011;38:180-1 pubmed publisher
  41. Kuemmerle Deschner J, Wittkowski H, Tyrrell P, Koetter I, Lohse P, Ummenhofer K, et al. Treatment of Muckle-Wells syndrome: analysis of two IL-1-blocking regimens. Arthritis Res Ther. 2013;15:R64 pubmed
    ..Canakinumab led to a sustained control of disease activity even after secondary failure of anakinra therapy. S100A12 may be a sensitive marker to detect subclinical disease activity. ..
  42. Parsons P, Moss M, Vannice J, Moore E, Moore F, Repine J. Circulating IL-1ra and IL-10 levels are increased but do not predict the development of acute respiratory distress syndrome in at-risk patients. Am J Respir Crit Care Med. 1997;155:1469-73 pubmed
    ..IL-4 was not detectable in any of the patient plasma samples measured. Thus, modulators of inflammation are increased in patients at risk for ARDS who die, but do not predict the development of the syndrome. ..
  43. Tran T, Pariente D, Lecron J, Delwail A, Taoufik Y, Meinzer U. Treatment of pediatric Erdheim-Chester disease with interleukin-1-targeting drugs. Arthritis Rheum. 2011;63:4031-2 pubmed publisher
  44. Fernández Paredes L, Casrouge A, Decalf J, de Andrés C, Villar L, Pérez de Diego R, et al. Multimarker risk stratification approach at multiple sclerosis onset. Clin Immunol. 2017;181:43-50 pubmed publisher
  45. Youssef J, Lazaro E, Blanco P, Viallard J. Blockade of interleukin 1 receptor in Still's disease affects activation of peripheral T-lymphocytes. J Rheumatol. 2008;35:2453-6 pubmed
  46. Bossi G. Mutant p53 and sIL-1Ra. Aging (Albany NY). 2015;7:742-3 pubmed
  47. Hahn K, Ho N, Yockey L, Kreuzberg S, Daub J, Rump A, et al. Treatment With Anakinra, a Recombinant IL-1 Receptor Antagonist, Unlikely to Induce Lasting Remission in Patients With CGD Colitis. Am J Gastroenterol. 2015;110:938-9 pubmed publisher
  48. . Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis. Lancet Diabetes Endocrinol. 2015;3:243-53 pubmed publisher
    ..The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. ..
  49. Sediva A, Polouckova A, Podrazil M, Fronkova E, Kalina T. Characterization of the B-cell compartment in a patient with Schnitzler syndrome. Scand J Rheumatol. 2011;40:158-60 pubmed publisher
  50. Yu G, Kubota H, Okita M, Maeda T. The anti-inflammatory and antioxidant effects of melatonin on LPS-stimulated bovine mammary epithelial cells. PLoS ONE. 2017;12:e0178525 pubmed publisher
    ..These results suggest that melatonin protects bMECs from LPS-induced inflammatory and oxidant stress damage and provide evidence that melatonin might have therapeutic utility in mastitis. ..
  51. Lytle K, Wong C, Jump D. Docosahexaenoic acid blocks progression of western diet-induced nonalcoholic steatohepatitis in obese Ldlr-/- mice. PLoS ONE. 2017;12:e0173376 pubmed publisher
    ..While these studies establish that DHA supplementation of the WD blocks WD-induced NASH progression, DHA alone does not promote full remission of diet-induced MetS or NASH. ..
  52. Petropoulou A, Robin M, Socie G, Galicier L. Transmission of familial Mediterranean fever mutation after bone marrow transplantation and successful treatment with anakinra. Transplantation. 2010;90:102-3 pubmed publisher
  53. Urien S, Bardin C, Bader Meunier B, Mouy R, Compeyrot Lacassagne S, Foissac F, et al. Anakinra pharmacokinetics in children and adolescents with systemic-onset juvenile idiopathic arthritis and autoinflammatory syndromes. BMC Pharmacol Toxicol. 2013;14:40 pubmed publisher
    ..Based on effects in SJIA, a prospective dosage adjustment was proposed based on a 0.4 mg/L Css target in order to obtain a CRP decrease to 10 mg/L or below. ..
  54. de Koning H, Schalkwijk J, Van der Meer J, Simon A. Successful canakinumab treatment identifies IL-1? as a pivotal mediator in Schnitzler syndrome. J Allergy Clin Immunol. 2011;128:1352-4 pubmed publisher