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Current Allergy and Asthma Reports

, Volume 11, Issue 5, pp 361–368 | Cite as

The Emerging Role of Interleukin-1β in Autoinflammatory Diseases

  • Thirusha Lane
  • Helen J. LachmannEmail author
Article
First Online:

Abstract

The autoinflammatory syndromes are a group of multisystem disorders characterized by recurrent episodes of fever and systemic inflammation affecting the eyes, joints, skin, and serosal surfaces in the absence of an immune reaction. Recent advances have revealed the importance of interleukin-1β, not only in the pathogenesis of many of these rare inherited diseases, but also in acquired diseases. The development and availability of anti–interleukin-1β therapeutics have introduced the possibility of proof-of-concept studies, which are likely to further widen this field.

Keywords

Interleukin-1 Inflammasome Autoinflammatory diseases Caspase-1 Cryopyrin NLRP3 CAPS Anakinra Rilonacept Canakinumab 
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Notes

Acknowledgment

Dr. Lachmann has received support from a European Union Framework 7 grant.

Disclosure

Dr. Lachmann has served as a consultant for Novartis and received honoraria and had travel/accommodations expenses covered by Novartis and Bristol-Myers Squibb.

Ms Lane reported no potential conflicts of interest relevant to this article.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    McDermott MF, Aksentijevich I, Galon J, et al. Germline mutations in the extracellular domains of the 55 kDa TNF receptor, TNFR1, define a family of dominantly inherited autoinflammatory syndromes. Cell. 1999;97:133–44.PubMedCrossRefGoogle Scholar
  2. 2.
    Cassel SL, Joly S, Sutterwala FS. The NLRP3 inflammasome: a sensor of immune danger signals. Semin Immunol. 2009;21(4):194–8.PubMedCrossRefGoogle Scholar
  3. 3.
    • Masters SL, Simon A, Aksentijevich I, et al. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol. [Research Support, Non-U.S. Gov’t Review]. 2009;27:621–68. This is a comprehensive review of the AIDs. PubMedCrossRefGoogle Scholar
  4. 4.
    McGonagle D, McDermott MF. A proposed classification of the immunological diseases. PLoS Medicine. 2006;3(8):1242–8.Google Scholar
  5. 5.
    Dinarello CA. Interleukin-1. Rev Infect Dis. 1984;6(1):51–95.PubMedCrossRefGoogle Scholar
  6. 6.
    Fantuzzi G, Dinarello CA. The inflammatory response in interleukin-1 beta-deficient mice: comparison with other cytokine-related knock-out mice. J Leukoc Biol. 1996;59(4):489–93.PubMedGoogle Scholar
  7. 7.
    • Dinarello CA. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood. 2011;117(14):3720–32. This is an excellent review of the role of IL-1 by the world expert. PubMedCrossRefGoogle Scholar
  8. 8.
    Tschopp J, Martinon F, Burns K. NALPs: a novel protein family involved in inflammation. Nat Rev Mol Cell Biol. 2003;4:95–104.PubMedCrossRefGoogle Scholar
  9. 9.
    Martinon F, Agostini L, Meylan E, et al. Identification of bacterial muramyl dipeptide as activator of the NALP3/cryopyrin inflammasome. Curr Biol. 2004;14:1929–34.PubMedCrossRefGoogle Scholar
  10. 10.
    Martinon F, Petrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440:237–41.PubMedCrossRefGoogle Scholar
  11. 11.
    Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87(6):2095–147.PubMedGoogle Scholar
  12. 12.
    Granowitz EV, Clark BD, Mancilla J, et al. Interleukin-1 receptor antagonist competitively inhibits the binding of interleukin-1 to the type II interleukin-1 receptor. J Biol Chem. 1991;266(22):14147–50.PubMedGoogle Scholar
  13. 13.
    Hannum CH, Wilcox CJ, Arend WP, et al. Interleukin-1 receptor antagonist activity of a human interleukin-1 inhibitor. Nature. 1990;343:336–40.PubMedCrossRefGoogle Scholar
  14. 14.
    Mertens M, Singh JA. Anakinra for rheumatoid arthritis: a systematic review. J Rheumatol. 2009;36(6):1118–25.PubMedCrossRefGoogle Scholar
  15. 15.
    Stahl N, Radin A, Mellis S. Rilonacept—CAPS and beyond. Ann NY Acad Sci. 2009;1182:124–34.PubMedCrossRefGoogle Scholar
  16. 16.
    Church LD, McDermott MF. Canakinumab, a fully-human mAb against IL-1beta for the potential treatment of inflammatory disorders. Curr Opin Mol Ther. 2009;11(1):81–9.PubMedGoogle Scholar
  17. 17.
    Owyang AM, Issafras H, Corbin J, et al. XOMA 052, a potent, high-affinity monoclonal antibody for the treatment of IL-1beta-mediated diseases. MAbs. 2011;3(1):49–60.PubMedCrossRefGoogle Scholar
  18. 18.
    Glaser RL, Goldbach-Mansky R. The spectrum of monogenic autoinflammatory syndromes: understanding disease mechanisms and use of targeted therapies. Curr Allergy Asthma Rep. 2008;8:288–98.PubMedCrossRefGoogle Scholar
  19. 19.
    Kile RL, Rusk HA. A case of cold urticaria with an unusual family history. JAMA. 1940;114:1067–8.Google Scholar
  20. 20.
    Leslie KS, Lachmann HJ, Bruning E, et al. Phenotype, genotype, and sustained response to anakinra in 22 patients with autoinflammatory disease associated with CIAS-1/NALP3 mutations. Arch Dermatol. 2006;142:1591–7.PubMedCrossRefGoogle Scholar
  21. 21.
    Goldbach-Mansky R, Dailey NJ, Canna SW, et al. Neonatal-onset multisystem inflammatory disease responsive to interleukin-1beta inhibition. N Engl J Med. 2006;355:581–92.PubMedCrossRefGoogle Scholar
  22. 22.
    Aksentijevich I, Nowak M, Mallah M, et al. De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID): a new member of the expanding family of pyrin-associated autoinflammatory diseases. Arthritis Rheum. 2002;46:3340–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Feldmann J, Prieur A-M, Quartier P, et al. Chronic infantile neurological cutaneous and articular syndrome is caused by mutations in CIAS1, a gene highly expressed in polymorphonuclear cells and chondrocytes. Am J Hum Genet. 2002;71:198–203.PubMedCrossRefGoogle Scholar
  24. 24.
    Hoffman HM, Mueller JL, Broide DH, et al. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet. 2001;29:301–5.PubMedCrossRefGoogle Scholar
  25. 25.
    Aksentijevich I, Putnam CD, Remmers EF, et al. The clinical continuum of cryopyrinopathies: novel CIAS1 mutations in North American patients and a new cryopyrin model. Arthritis Rheum. 2007;56(4):1273–85.PubMedCrossRefGoogle Scholar
  26. 26.
    Hoffman HM, Rosengren S, Boyle DL, et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist. Lancet. 2004;364(9447):1779–85.PubMedCrossRefGoogle Scholar
  27. 27.
    Ross JB, Finlayson LA, Klotz PJ, et al. Use of anakinra (Kineret) in the treatment of familial cold autoinflammatory syndrome with a 16-month follow-up. J Cutan Med Surg. 2008;12:8–16.PubMedGoogle Scholar
  28. 28.
    Neven B, Marvillet I, Terrada C, et al. Long-term efficacy of the interleukin-1 receptor antagonist anakinra in ten patients with neonatal-onset multisystem inflammatory disease/chronic infantile neurologic, cutaneous, articular syndrome. Arthritis Rheum. 2010;62(1):258–67.PubMedCrossRefGoogle Scholar
  29. 29.
    Rigante D, Leone A, Marrocco R, et al. Long-term response after 6-year treatment with anakinra and onset of focal bone erosion in neonatal-onset multisystem inflammatory disease (NOMID/CINCA). Rheumatol Int. 2011 Jan 15. [Epub ahead of print].Google Scholar
  30. 30.
    Kuemmerle-Deschner JB, Tyrrell PN, Koetter I, et al. Efficacy and safety of anakinra therapy in pediatric and adult patients with the autoinflammatory Muckle-Wells syndrome. Arthritis Rheum. 2011;63(3):840–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Goldbach-Mansky R, Shroff SD, Wilson M, et al. A pilot study to evaluate the safety and efficacy of the long-acting interleukin-1 inhibitor rilonacept (interleukin-1 Trap) in patients with familial cold autoinflammatory syndrome. Arthritis Rheum. 2008;58:2432–42.PubMedCrossRefGoogle Scholar
  32. 32.
    Hoffman HM, Throne ML, Amar NJ, et al. Efficacy and safety of rilonacept (interleukin-1 trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008;58:2443–52.PubMedCrossRefGoogle Scholar
  33. 33.
    Hoffman HM, Nadler DR, Brooks PW, et al. Rilonacept: Long-term safety profile in patients with cryopyrin-associated periodic syndromes (CAPS). Arthritis Rheum. 2009;60 Suppl 10:1237.Google Scholar
  34. 34.
    Lachmann HJ, Lowe P, Felix SD, et al. In vivo regulation of interleukin 1beta in patients with cryopyrin-associated periodic syndromes. J Exp Med. 2009;206:1029–36.PubMedCrossRefGoogle Scholar
  35. 35.
    Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, et al. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009;360(23):2416–25.PubMedCrossRefGoogle Scholar
  36. 36.
    Meinzer U, Quartier P, Alexandra JF, et al. Interleukin-1 targeting drugs in familial Mediterranean fever: a case series and a review of the literature. Semin Arthritis Rheum. 2011 Jan 28.Google Scholar
  37. 37.
    Chae JJ, Wood G, Masters SL, et al. The B30.2 domain of pyrin, the familial Mediterranean fever protein, interacts directly with caspase-1 to modulate IL-1beta production. Proc Natl Acad Sci USA. 2006;103:9982–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Kallinich T, Haffner D, Niehues T, et al. Colchicine use in children and adolescents with familial Mediterranean fever: literature review and consensus statement. Pediatrics. 2007;119(2):e474–83.PubMedCrossRefGoogle Scholar
  39. 39.
    Moser C, Pohl G, Haslinger I, et al. Successful treatment of familial Mediterranean fever with anakinra and outcome after renal transplantation. Nephrol Dial Transplant. 2009;24:676–8.PubMedCrossRefGoogle Scholar
  40. 40.
    Alpay N, Sumnu A, Caliskan Y, et al. Efficacy of anakinra treatment in a patient with colchicine-resistant familial Mediterranean fever. Rheumatol Int. 2010 Apr 13. [Epub ahead of print].Google Scholar
  41. 41.
    Calligaris L, Marchetti F, Tommasini A, et al. The efficacy of anakinra in an adolescent with colchicine-resistant familial Mediterranean fever. Eur J Pediatr. 2008;167:695–6.PubMedCrossRefGoogle Scholar
  42. 42.
    Roldan R, Ruiz AM, Miranda MD, et al. Anakinra: new therapeutic approach in children with familial Mediterranean fever resistant to colchicine. Joint Bone Spine. 2008;75:504–5.PubMedCrossRefGoogle Scholar
  43. 43.
    Todd I, Radford PM, Daffa N, et al. Mutant tumor necrosis factor receptor associated with tumor necrosis factor receptor-associated periodic syndrome is altered antigenically and is retained within patients’ leukocytes. Arthritis Rheum. 2007;56:2765–73.PubMedCrossRefGoogle Scholar
  44. 44.
    Rebelo SL, Bainbridge SE, Amel-Kashipaz MR, et al. Modeling of tumor necrosis factor receptor superfamily 1A mutants associated with tumor necrosis factor receptor-associated periodic syndrome indicates misfolding consistent with abnormal function. Arthritis Rheum. 2006;54:2674–87.PubMedCrossRefGoogle Scholar
  45. 45.
    D’Osualdo A, Ferlito F, Prigione I, et al. Neutrophils from patients with TNFRSF1A mutations display resistance to tumor necrosis factor-induced apoptosis: pathogenetic and clinical implications. Arthritis Rheum. 2006;54:998–1008.PubMedCrossRefGoogle Scholar
  46. 46.
    Nedjai B, Hitman GA, Yousaf N, et al. Abnormal tumor necrosis factor receptor I cell surface expression and NF-kappaB activation in tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum. 2008;58:273–83.PubMedCrossRefGoogle Scholar
  47. 47.
    Pettersson T, Kantonen J, Matikainen S, et al. Setting up TRAPS. Ann Med. 2011 Feb 1. [Epub ahead of print].Google Scholar
  48. 48.
    Simon A, Bodar EJ, van der Hilst JC, et al. Beneficial response to interleukin 1 receptor antagonist in traps. Am J Med. 2004;117:208–10.PubMedCrossRefGoogle Scholar
  49. 49.
    Jacobelli S, Andre M, Alexandra JF, et al. Failure of anti-TNF therapy in TNF receptor 1-associated periodic syndrome (TRAPS). Rheumatology (Oxford). 2007;46:1211–2.CrossRefGoogle Scholar
  50. 50.
    Drewe E, Powell RJ, McDermott EM. Comment on: Failure of anti-TNF therapy in TNF receptor 1-associated periodic syndrome (TRAPS). Rheumatology (Oxford). 2007;46:1865–6.CrossRefGoogle Scholar
  51. 51.
    Gattorno M, Pelagatti MA, Meini A, et al. Persistent efficacy of anakinra in patients with tumor necrosis factor receptor-associated periodic syndrome. Arthritis Rheum. 2008;58:1516–20.PubMedCrossRefGoogle Scholar
  52. 52.
    Cuisset L, Drenth JP, Simon A, et al. Molecular analysis of MVK mutations and enzymatic activity in hyper-IgD and periodic fever syndrome. Eur J Hum Genet. 2001;9:260–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Simon A, Cuisset L, Vincent MF, et al. Molecular analysis of the mevalonate kinase gene in a cohort of patients with the hyper-IgD and periodic fever syndrome: its application as a diagnostic tool. Ann Intern Med. 2001;135(5):338–43.PubMedGoogle Scholar
  54. 54.
    Normand S, Massonnet B, Delwail A, et al. Specific increase in caspase-1 activity and secretion of IL-1 family cytokines: a putative link between mevalonate kinase deficiency and inflammation. Eur Cytokine Netw. 2009;20(3):101–7.PubMedGoogle Scholar
  55. 55.
    van der Hilst JC, Bodar EJ, Barron KS, et al. Long-term follow-up, clinical features, and quality of life in a series of 103 patients with hyperimmunoglobulinemia D syndrome. Medicine (Baltimore). 2008;87:301–10.CrossRefGoogle Scholar
  56. 56.
    Cailliez M, Garaix F, Rousset-Rouviere C, et al. Anakinra is safe and effective in controlling hyperimmunoglobulinaemia D syndrome-associated febrile crisis. J Inherit Metab Dis. 2006;29(6):763.PubMedCrossRefGoogle Scholar
  57. 57.
    Wise CA, Gillum JD, Seidman CE, et al. Mutations in CD2BP1 disrupt binding to PTP PEST and are responsible for PAPA syndrome, an autoinflammatory disorder. Hum Mol Genet. 2002;11:961–9.PubMedCrossRefGoogle Scholar
  58. 58.
    Brenner M, Ruzicka T, Plewig G, et al. Targeted treatment of pyoderma gangrenosum in PAPA (pyogenic arthritis, pyoderma gangrenosum and acne) syndrome with the recombinant human interleukin-1 receptor antagonist anakinra. Br J Dermatol. 2009;161:1199–201.PubMedCrossRefGoogle Scholar
  59. 59.
    Dierselhuis MP, Frenkel J, Wulffraat NM, et al. Anakinra for flares of pyogenic arthritis in PAPA syndrome. Rheumatology (Oxford). 2005;44(3):406–8.CrossRefGoogle Scholar
  60. 60.
    Aksentijevich I, Masters SL, Ferguson PJ, et al. An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med. 2009;360:2426–37.PubMedCrossRefGoogle Scholar
  61. 61.
    Lequerre T, Quartier P, Rosellini D, et al. Interleukin-1 receptor antagonist (anakinra) treatment in patients with systemic-onset juvenile idiopathic arthritis or adult onset Still disease: preliminary experience in France. Ann Rheum Dis. 2008;67(3):302–8.PubMedCrossRefGoogle Scholar
  62. 62.
    Pascual V, Allantaz F, Arce E, et al. Role of interleukin-1 (IL-1) in the pathogenesis of systemic onset juvenile idiopathic arthritis and clinical response to IL-1 blockade. J Exp Med. 2005;201(9):1479–86.PubMedCrossRefGoogle Scholar
  63. 63.
    Zeft A, Hollister R, LaFleur B, et al. Anakinra for systemic juvenile arthritis: the Rocky Mountain experience. J Clin Rheumatol. 2009;15(4):161–4.PubMedCrossRefGoogle Scholar
  64. 64.
    Gattorno M, Piccini A, Lasiglie D, et al. The pattern of response to anti-interleukin-1 treatment distinguishes two subsets of patients with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum. 2008;58(5):1505–15.PubMedCrossRefGoogle Scholar
  65. 65.
    Quartier P, Allantaz F, Cimaz R, et al. A multicentre, randomised, double-blind, placebo-controlled trial with the interleukin-1 receptor antagonist anakinra in patients with systemic-onset juvenile idiopathic arthritis (ANAJIS trial). Ann Rheum Dis. 2011;70(5):747–54.PubMedCrossRefGoogle Scholar
  66. 66.
    Lovell DJ, Giannini EH, Kimura Y, et al. Preliminary evidence for sustained bioactivity of IL-1 Trap (rilonacept), a long acting IL-1 inhibitor, in systemic juvenile idiopathic arthritis (SJIA). Arthritis Rheum. 2007;56(Suppl):S514–5.Google Scholar
  67. 67.
    Lovell DJ, Giannini EH, Kimura Y, et al. Long-term safety and efficacy of rilonacept in patients with systemic juvenile idiopathic arthritis (SJIA). Arthritis Rheum. 2009;60(Suppl):S768.Google Scholar
  68. 68.
    Ruperto N, Quartier P, Wulffraat N, et al. Phase II trial with canakinumab (ACZ885) to evaluate safety and preliminary efficacy in children with systemic juvenile idiopathic arthritis (SJIA). Acta Paediatr. 2009;98:223–4.Google Scholar
  69. 69.
    Hoffman HM, Wanderer AA. Inflammasome and IL-1beta-mediated disorders. Curr Allergy Asthma Rep. 2010;10(4):229–35.PubMedCrossRefGoogle Scholar
  70. 70.
    de Koning HD, Bodar EJ, van der Meer JW, et al. Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum. 2007;37:137–48.PubMedCrossRefGoogle Scholar
  71. 71.
    So A, De Smedt T, Revaz S, et al. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther. 2007;9:R28.PubMedCrossRefGoogle Scholar
  72. 72.
    Schlesinger N, Mysler E, Lin HY, et al. Canakinumab reduces the risk of acute gouty arthritis flares during initiation of allopurinol treatment: results of a double-blind, randomised study. Ann Rheum Dis. 2011 May 3.Google Scholar
  73. 73.
    • Schroder K, Zhou R, Tschopp J. The NLRP3 inflammasome: a sensor for metabolic danger? Science. 2010;327(5963):296–300. This is an up-to-date review of the function of the inflammasome and its wider significance. PubMedCrossRefGoogle Scholar
  74. 74.
    Nishikawa T, Kukidome D, Sonoda K, et al. Impact of mitochondrial ROS production in the pathogenesis of insulin resistance. Diabetes Res Clin Pract. 2007;77 Suppl 1:S161–4.PubMedCrossRefGoogle Scholar
  75. 75.
    Boni-Schnetzler M, Thorne J, Parnaud G, et al. Increased interleukin (IL)-1beta messenger ribonucleic acid expression in beta -cells of individuals with type 2 diabetes and regulation of IL-1beta in human islets by glucose and autostimulation. J Clin Endocrinol Metab. 2008;93(10):4065–74.PubMedCrossRefGoogle Scholar
  76. 76.
    Larsen CM, Faulenbach M, Vaag A, et al. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care. 2009;32:1663–8.PubMedCrossRefGoogle Scholar
  77. 77.
    Larsen A. The relation of radiographic changes to serum acute-phase proteins and rheumatoid factor in 200 patients with rheumatoid arthritis. Scand J Rheumatol. 1988;17:123–9.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.National Amyloidosis Centre, Division of MedicineUCL Medical School, Royal Free CampusLondonUK

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