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Cited by 2,248Inflammasome and immune disordersImmune Response and InflammationCytokine Signaling Pathways and Interactions

Interleukin-1 in the pathogenesis and treatment of inflammatory diseases

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Dinarello, Charles A.·2011·Blood
DOI 10.1182/blood-2010-07-273417PMC PMC3083294
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Abstract

More than any other cytokine family, the IL-1 family of ligands and receptors is primarily associated with acute and chronic inflammation. The cytosolic segment of each IL-1 receptor family member contains the Toll-IL-1-receptor domain. This domain is also present in each Toll-like receptor, the receptors that respond to microbial products and viruses. Since Toll-IL-1-receptor domains are functional for both receptor families, responses to the IL-1 family are fundamental to innate immunity. Of the 11 members of the IL-1 family, IL-1β has emerged as a therapeutic target for an expanding number of systemic and local inflammatory conditions called autoinflammatory diseases. For these, neutralization of IL-1β results in a rapid and sustained reduction in disease severity. Treatment for autoimmune diseases often includes immunosuppressive drugs whereas neutralization of IL-1β is mostly anti-inflammatory. Although some autoinflammatory diseases are due to gain-of-function mutations for caspase-1 activity, common diseases such as gout, type 2 diabetes, heart failure, recurrent pericarditis, rheumatoid arthritis, and smoldering myeloma also are responsive to IL-1β neutralization. This review summarizes acute and chronic inflammatory diseases that are treated by reducing IL-1β activity and proposes that disease severity is affected by the anti-inflammatory members of the IL-1 family of ligands and receptors.

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  • Mitochondria are involved both in recognition of pathogens and in many mechanisms of inflammatory response, inducing recruitment of proinflammatory cytokines.

    “mitochondria are involved both in the recognition of pathogens and in many mechanisms of inflammatory response, inducing the subsequent recruitment of several proinflammatory cytokines [52].”

    From Effects of Mangiferin on LPS-Induced Inflammation and SARS-CoV-2 Viral Adsorption in Human Lung Cells (2022) · cites this paper as [52]

    The Introduction (page unavailable) says mitochondrial reactive oxygen species may contribute to caspase-1 activation, a pathway involved in IL-1β secretion. It does not say mitochondria recognize pathogens or induce the recruitment of several proinflammatory cytokines; its account of pathogen-product recognition concerns TLRs instead. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • IL-1 signaling is closely linked to chronic inflammatory diseases and plays a critical role in the activation of inflammatory myelopoiesis.

    “IL-1β is produced in response to a wide range of physiological insults, and IL-1 signaling is closely linked to a wide variety of chronic inflammatory diseases, where it plays a critical role in the activation of inflammatory myelopoiesis (Ueda et al., 2009; Dinarello, 2011; Mirantes et al., 2014; Pietras, 2017).”

    From PU.1 is required to restrain myelopoiesis during chronic inflammatory stress (2023) · cites this paper as Dinarello, 2011

    The Abstract links the IL-1 family to acute and chronic inflammation and lists several inflammatory diseases responsive to IL-1β blockade. The passages on bone marrow and myeloid cells do not establish that IL-1 signaling plays a critical role in activating inflammatory myelopoiesis, so that part of the attributed claim is unsupported. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

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  1. [1]Dinarello CA. Biological basis for interleukin-1 in disease. Blood. 1996;87(6):2095–2147. [PubMed] [Google Scholar]
  2. [2]Opal SM, Fisher CJJ, Dhainaut JF, et al. Confirmatory interleukin-1 receptor antagonist trial in severe sepsis: a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Crit Care Med. 1997;25(7):1115–1124. doi: 10.1097/00003246-199707000-00010. [DOI] [PubMed] [Google Scholar] · DOI
  3. [3]Eichacker PQ, Parent C, Kalil A, et al. Risk and the efficacy of antiinflammatory agents: retrospective and confirmatory studies of sepsis. Am J Respir Crit Care Med. 2002;166(9):1197–1205. doi: 10.1164/rccm.200204-302OC. [DOI] [PubMed] [Google Scholar] · DOI
  4. [4]Lust JA, Lacy MQ, Zeldenrust SR, et al. Induction of a chronic disease state in patients with smoldering or indolent multiple myeloma by targeting interleukin 1beta-induced interleukin 6 production and the myeloma proliferative component. Mayo Clin Proc. 2009;84(2):114–122. doi: 10.4065/84.2.114. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  5. [5]Simon A, van der Meer JW. Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R86–98. doi: 10.1152/ajpregu.00504.2006. [DOI] [PubMed] [Google Scholar] · DOI
  6. [6]Masters SL, Simon A, Aksentijevich I, Kastner DL. Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol. 2009;27:621–668. doi: 10.1146/annurev.immunol.25.022106.141627. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  7. [8]Weber A, Wasiliew P, Kracht M. Interleukin-1 (IL-1) pathway. Sci Signal. 2010;3:cm1. doi: 10.1126/scisignal.3105cm1. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  8. [10]Werman A, Werman-Venkert R, White R, et al. The precursor form of IL-1alpha is an intracrine proinflammatory activator of transcription. Proc Natl Acad Sci U S A. 2004;101(8):2434–2439. doi: 10.1073/pnas.0308705101. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  9. [11]Sharma S, Kulk N, Nold MF, et al. The IL-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokines. J Immunol. 2008;180(8):5477–5482. doi: 10.4049/jimmunol.180.8.5477. [DOI] [PubMed] [Google Scholar] · DOI
  10. [12]Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA. IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol. 2010;11(11):1014–1022. doi: 10.1038/ni.1944. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  11. [13]O'Neill LA. The interleukin-1 receptor/Toll-like receptor superfamily: 10 years of progress. Immunol Rev. 2008;226:10–18. doi: 10.1111/j.1600-065X.2008.00701.x. [DOI] [PubMed] [Google Scholar] · DOI
  12. [14]Heguy A, Baldari C, Bush K, et al. Internalization and nuclear localization of interleukin 1 are not sufficient for function. Cell Growth Differ. 1991;2(7):311–315. [PubMed] [Google Scholar]
  13. [15]van der Meer JWM, Barza M, Wolff SM, Dinarello CA. A low dose of recombinant interleukin 1 protects granulocytopenic mice from lethal gram-negative infection. Proc Natl Acad Sci U S A. 1988;85(5):1620–1623. doi: 10.1073/pnas.85.5.1620. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  14. [16]Rosenwasser LJ, Dinarello CA, Rosenthal AS. Adherent cell function in murine T-lymphocyte antigen recognition, IV: enhancement of murine T-cell antigen recognition by human leukocytic pyrogen. J Exp Med. 1979;150(3):709–714. doi: 10.1084/jem.150.3.709. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  15. [17]Garlanda C, Anders HJ, Mantovani A. TIR8/SIGIRR: an IL-1R/TLR family member with regulatory functions in inflammation and T cell polarization. Trends Immunol. 2009;30(9):439–446. doi: 10.1016/j.it.2009.06.001. [DOI] [PubMed] [Google Scholar] · DOI
  16. [18]Smith DE, Lipsky BP, Russell C, et al. A central nervous system-restricted isoform of the interleukin-1 receptor accessory protein modulates neuronal responses to interleukin-1. Immunity. 2009;30(6):817–831. doi: 10.1016/j.immuni.2009.03.020. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  17. [19]O'Neill LA, Bryant CE, Doyle SL. Therapeutic targeting of toll-like receptors for infectious and inflammatory diseases and cancer. Pharmacol Rev. 2009;61(2):177–197. doi: 10.1124/pr.109.001073. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  18. [20]Arslan F, Smeets MB, O'Neill LA, et al. Myocardial ischemia/reperfusion injury is mediated by leukocytic toll-like receptor-2 and reduced by systemic administration of a novel anti-toll-like receptor-2 antibody. Circulation. 2010;121(1):80–90. doi: 10.1161/CIRCULATIONAHA.109.880187. [DOI] [PubMed] [Google Scholar] · DOI
  19. [21]van Asseldonk EJ, Stienstra R, Koenen TB, et al. The effect of the interleukin-1 cytokine family members IL-1F6 and IL-1F8 on adipocyte differentiation. Obesity. 2010;18(11):2234–2236. doi: 10.1038/oby.2010.55. [DOI] [PubMed] [Google Scholar] · DOI
  20. [22]Blumberg H, Dinh H, Trueblood ES, et al. Opposing activities of two novel members of the IL-1 ligand family regulate skin inflammation. J Exp Med. 2007;204(11):2603–2614. doi: 10.1084/jem.20070157. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  21. [23]Colotta F, Re F, Muzio M, et al. Interleukin-1 type II receptor: a decoy target for IL-1 that is regulated by IL-4. Science. 1993;261(5120):472–475. doi: 10.1126/science.8332913. [DOI] [PubMed] [Google Scholar] · DOI
  22. [24]Smeets RL, Joosten LA, Arntz OJ, et al. Soluble interleukin-1 receptor accessory protein ameliorates collagen-induced arthritis by a different mode of action from that of interleukin-1 receptor antagonist. Arthritis Rheum. 2005;52(7):2202–2211. doi: 10.1002/art.21108. [DOI] [PubMed] [Google Scholar] · DOI
  23. [25]Vambutas A, DeVoti J, Goldofsky E, Gordon M, Lesser M, Bonagura V. Alternate splicing of interleukin-1 receptor type II (IL1R2) in vitro correlates with clinical glucocorticoid responsiveness in patients with AIED. PLoS One. 2009;4:e5293. doi: 10.1371/journal.pone.0005293. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  24. [26]Akoum A, Al-Akoum M, Lemay A, Maheux R, Leboeuf M. Imbalance in the peritoneal levels of interleukin 1 and its decoy inhibitory receptor type II in endometriosis women with infertility and pelvic pain. Fertil Steril. 2008;89(6):1618–1624. doi: 10.1016/j.fertnstert.2007.06.019. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  25. [27]Wald D, Qin J, Zhao Z, et al. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol. 2003;4(9):920–927. doi: 10.1038/ni968. [DOI] [PubMed] [Google Scholar] · DOI
  26. [28]Garlanda C, Riva F, Polentarutti N, et al. Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family. Proc Natl Acad Sci U S A. 2004;101(10):3522–3526. doi: 10.1073/pnas.0308680101. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  27. [29]Bulek K, Swaidani S, Qin J, et al. The essential role of single Ig IL-1 receptor-related molecule/Toll IL-1R8 in regulation of Th2 immune response. J Immunol. 2009;182(5):2601–2609. doi: 10.4049/jimmunol.0802729. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  28. [30]Lech M, Avila-Ferrufino A, Allam R, et al. Resident dendritic cells prevent postischemic acute renal failure by help of single Ig IL-1 receptor-related protein. J Immunol. 2009;183(6):4109–4118. doi: 10.4049/jimmunol.0900118. [DOI] [PubMed] [Google Scholar] · DOI
  29. [31]Melnikov VY, Ecder T, Fantuzzi G, et al. Impaired IL-18 processing protects caspase-1-deficient mice from ischemic acute renal failure. J Clin Invest. 2001;107(9):1145–1152. doi: 10.1172/JCI12089. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  30. [32]Ferretti M, Casini-Raggi V, Pizarro TT, Eisenberg SP, Nast CC, Cominelli F. Neutralization of endogenous IL-1 receptor antagonist exacerbates and prolongs inflammation in rabbit immune colitis. J Clin Invest. 1994;94(1):449–453. doi: 10.1172/JCI117345. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  31. [33]Horai R, Saijo S, Tanioka H, et al. Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J Exp Med. 2000;191(2):313–320. doi: 10.1084/jem.191.2.313. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  32. [34]Nicklin MJ, Hughes DE, Barton JL, Ure JM, Duff GW. Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene. J Exp Med. 2000;191(2):303–312. doi: 10.1084/jem.191.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  33. [35]Krelin Y, Voronov E, Dotan S, et al. Interleukin-1beta-driven inflammation promotes the development and invasiveness of chemical carcinogen-induced tumors. Cancer Res. 2007;67(3):1062–1071. doi: 10.1158/0008-5472.CAN-06-2956. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  34. [36]Dinarello CA. Why not treat human cancer with interleukin-1 blockade? Cancer Metastasis Rev. 2010;29(2):317–329. doi: 10.1007/s10555-010-9229-0. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  35. [37]Larsen CM, Faulenbach M, Vaag A, Ehses JA, Donath MY, Mandrup-Poulsen T. Sustained effects of interleukin-1 receptor antagonist treatment in type 2 diabetes. Diabetes Care. 2009;32(9):1663–1668. doi: 10.2337/dc09-0533. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  36. [38]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(23):2426–2437. doi: 10.1056/NEJMoa0807865. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  37. [39]Reddy S, Jia S, Geoffrey R, et al. An autoinflammatory disease due to homozygous deletion of the IL1RN locus. N Engl J Med. 2009;360(23):2438–2444. doi: 10.1056/NEJMoa0809568. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  38. [40]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(5):1029–1036. doi: 10.1084/jem.20082481. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  39. [41]Pascual V, Allantaz F, Arce E, Punaro M, Banchereau J. 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):1479–1486. doi: 10.1084/jem.20050473. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  40. [42]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(6):581–592. doi: 10.1056/NEJMoa055137. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  41. [43]Gattorno M, Tassi S, Carta S, et al. Pattern of interleukin-1beta secretion in response to lipopolysaccharide and ATP before and after interleukin-1 blockade in patients with CIAS1 mutations. Arthritis Rheum. 2007;56(9):3138–3148. doi: 10.1002/art.22842. [DOI] [PubMed] [Google Scholar] · DOI
  42. [44]Hoffman HM, Rosengren S, Boyle DL, et al. Prevention of cold-associated acute inflammation in familial cold autoinflammatory syndrome by interleukin-1 receptor antagonist prevents. Lancet. 2004;364(9447):1779–1785. doi: 10.1016/S0140-6736(04)17401-1. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  43. [45]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):1505–1515. doi: 10.1002/art.23437. [DOI] [PubMed] [Google Scholar] · DOI
  44. [46]Eiling E, Moller M, Kreiselmaier I, Brasch J, Schwarz T. Schnitzler syndrome: treatment failure to rituximab but response to anakinra. J Am Acad Dermatol. 2007;57(2):361–364. doi: 10.1016/j.jaad.2007.03.036. [DOI] [PubMed] [Google Scholar] · DOI
  45. [47]Goldbach-Mansky R, Kastner DL. Autoinflammation: the prominent role of IL-1 in monogenic autoinflammatory diseases and implications for common illnesses. J Allergy Clin Immunol. 2009;124(6):1141–1149. doi: 10.1016/j.jaci.2009.11.016. quiz 1150–1141. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  46. [48]Hawkins PN, Lachmann HJ, Aganna E, McDermott MF. Spectrum of clinical features in Muckle-Wells syndrome and response to anakinra. Arthr Rheumat. 2004;50(2):607–612. doi: 10.1002/art.20033. [DOI] [PubMed] [Google Scholar] · DOI
  47. [49]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(8):2443–2452. doi: 10.1002/art.23687. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  48. [50]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):2416–2425. doi: 10.1056/NEJMoa0810787. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  49. [51]Netea MG, Nold-Petry CA, Nold MF, et al. Differential requirement for the activation of the inflammasome for processing and release of IL-1beta in monocytes and macrophages. Blood. 2009;113(10):2324–2335. doi: 10.1182/blood-2008-03-146720. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  50. [53]Andrei C, Margiocco P, Poggi A, Lotti LV, Torrisi MR, Rubartelli A. Phospholipases C and A2 control lysosome-mediated IL-1 beta secretion: implications for inflammatory processes. Proc Natl Acad Sci U S A. 2004;101(26):9745–9750. doi: 10.1073/pnas.0308558101. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  51. [54]Perregaux DG, McNiff P, Laliberte R, Conklyn M, Gabel CA. ATP acts as an agonist to promote stimulus-induced secretion of IL-1 beta and IL-18 in human blood. J Immunol. 2000;165(8):4615–4623. doi: 10.4049/jimmunol.165.8.4615. [DOI] [PubMed] [Google Scholar] · DOI
  52. [55]Solle M, Labasi J, Perregaux DG, et al. Altered cytokine production in mice lacking P2X(7) receptors. J Biol Chem. 2001;276(1):125–132. doi: 10.1074/jbc.M006781200. [DOI] [PubMed] [Google Scholar] · DOI
  53. [56]Agostini L, Martinon F, Burns K, McDermott MF, Hawkins PN, Tschopp J. NALP3 forms an IL-1β processing inflammasome with increased activity in Muckle-Wells auto-inflammatory disorder. Immunity. 2004;20(3):319–325. doi: 10.1016/s1074-7613(04)00046-9. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  54. [57]Hoffman HM, Mueller JL, Broide DH, Wanderer AA, Kolodner RD. Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle-Wells syndrome. Nat Genet. 2001;29(3):301–305. doi: 10.1038/ng756. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  55. [58]Bergsbaken T, Fink SL, Cookson BT. Pyroptosis: host cell death and inflammation. Nat Rev Microbiol. 2009;7(2):99–109. doi: 10.1038/nrmicro2070. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  56. [59]Dinarello CA, Ikejima T, Warner SJ, et al. Interleukin 1 induces interleukin 1. I. Induction of circulating interleukin 1 in rabbits in vivo and in human mononuclear cells in vitro. J Immunol. 1987;139(6):1902–1910. [PubMed] [Google Scholar]
  57. [60]Fantuzzi G, Ku G, Harding MW, et al. Response to local inflammation of IL-1beta converting enzyme-deficient mice. J Immunol. 1997;158(4):1818–1824. [PubMed] [Google Scholar]
  58. [61]Joosten LA, Netea MG, Fantuzzi G, et al. Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta. Arthritis Rheum. 2009;60(12):3651–3662. doi: 10.1002/art.25006. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  59. [62]Guma M, Ronacher L, Liu-Bryan R, Takai S, Karin M, Corr M. Caspase 1-independent activation of interleukin-1beta in neutrophil-predominant inflammation. Arthritis Rheum. 2009;60(12):3642–3650. doi: 10.1002/art.24959. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  60. [64]Meissner F, Molawi K, Zychlinsky A. Superoxide dismutase 1 regulates caspase-1 and endotoxic shock. Nat Immunol. 2008;9(8):866–872. doi: 10.1038/ni.1633. [DOI] [PubMed] [Google Scholar] · DOI
  61. [65]van de Veerdonk FL, Smeekens SP, Joosten LA, et al. Reactive oxygen species-independent activation of the IL-1beta inflammasome in cells from patients with chronic granulomatous disease. Proc Natl Acad Sci U S A. 2010;107(7):3030–3033. doi: 10.1073/pnas.0914795107. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  62. [66]Meissner F, Seger RA, Moshous D, Fischer A, Reichenbach J, Zychlinsky A. Inflammasome activation in NADPH oxidase defective mononuclear phagocytes from patients with chronic granulomatous disease. Blood. 2010;116(9):1570–1573. doi: 10.1182/blood-2010-01-264218. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  63. [67]Tassi S, Carta S, Delfino L, et al. Altered redox state of monocytes from cryopyrin-associated periodic syndromes causes accelerated IL-1beta secretion. Proc Natl Acad Sci U S A. 2010;107(21):9789–9794. doi: 10.1073/pnas.1000779107. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  64. [69]Eigenbrod T, Park JH, Harder J, Iwakura Y, Nunez G. Cutting edge: critical role for mesothelial cells in necrosis-induced inflammation through the recognition of IL-1 alpha released from dying cells. J Immunol. 2008;181(12):8194–8198. doi: 10.4049/jimmunol.181.12.8194. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  65. [70]Cohen I, Rider P, Carmi Y, et al. Differential release of chromatin-bound IL-1alpha discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation. Proc Natl Acad Sci U S A. 2010;107(6):2574–2579. doi: 10.1073/pnas.0915018107. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  66. [71]Pollock AS, Turck J, Lovett DH. The prodomain of interleukin 1alpha interacts with elements of the RNA processing apparatus and induces apoptosis in malignant cells. FASEB J. 2003;17(2):203–213. doi: 10.1096/fj.02-0602com. [DOI] [PubMed] [Google Scholar] · DOI
  67. [72]Abbate A, Salloum FN, Vecile E, et al. Anakinra, a recombinant human interleukin-1 receptor antagonist, inhibits apoptosis in experimental acute myocardial infarction. Circulation. 2008;117(20):2670–2683. doi: 10.1161/CIRCULATIONAHA.107.740233. [DOI] [PubMed] [Google Scholar] · DOI
  68. [73]Di Paolo NC, Miao EA, Iwakura Y, et al. Virus binding to a plasma membrane receptor triggers interleukin-1 alpha-mediated proinflammatory macrophage response in vivo. Immunity. 2009;31(1):110–121. doi: 10.1016/j.immuni.2009.04.015. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  69. [74]Kelk P, Claesson R, Chen C, Sjostedt A, Johansson A. IL-1beta secretion induced by Aggregatibacter (Actinobacillus) actinomycetemcomitans is mainly caused by the leukotoxin. Int J Med Microbiol. 2008;298(5–6):529–541. doi: 10.1016/j.ijmm.2007.06.005. [DOI] [PubMed] [Google Scholar] · DOI
  70. [76]Ben-Sasson SZ, Hu-Li J, Quiel J, et al. IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc Natl Acad Sci U S A. 2009;106(17):7119–7124. doi: 10.1073/pnas.0902745106. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  71. [77]van de Veerdonk FL, Teirlinck AC, Kleinnijenhuis J, et al. Mycobacterium tuberculosis induces IL-17A responses through TLR4 and dectin-1 and is critically dependent on endogenous IL-1. J Leukoc Biol. 2010;88(2):227–232. doi: 10.1189/jlb.0809550. [DOI] [PubMed] [Google Scholar] · DOI
  72. [78]Joosten LA. Excessive interleukin-1 signaling determines the development of Th1 and Th17 responses in chronic inflammation. Arthritis Rheum. 2010;62(2):320–322. doi: 10.1002/art.27242. [DOI] [PubMed] [Google Scholar] · DOI
  73. [79]Chung Y, Chang SH, Martinez GJ, et al. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity. 2009;30(4):576–587. doi: 10.1016/j.immuni.2009.02.007. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  74. [80]Koenders MI, Devesa I, Marijnissen RJ, et al. Interleukin-1 drives pathogenic Th17 cells during spontaneous arthritis in interleukin-1 receptor antagonist-deficient mice. Arthritis Rheum. 2008;58(11):3461–3470. doi: 10.1002/art.23957. [DOI] [PubMed] [Google Scholar] · DOI
  75. [81]Nakae S, Saijo S, Horai R, Sudo K, Mori S, Iwakura Y. IL-17 production from activated T cells is required for the spontaneous development of destructive arthritis in mice deficient in IL-1 receptor antagonist. Proc Natl Acad Sci U S A. 2003;100(10):5986–5990. doi: 10.1073/pnas.1035999100. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  76. [82]Lamacchia C, Palmer G, Seemayer CA, Talabot-Ayer D, Gabay C. Enhanced Th1 and Th17 responses and arthritis severity in mice with a deficiency of myeloid cell-specific interleukin-1 receptor antagonist. Arthritis Rheum. 2010;62(2):452–462. doi: 10.1002/art.27235. [DOI] [PubMed] [Google Scholar] · DOI
  77. [83]van de Veerdonk FL, Lauweys B, DiPadova F, et al. The anti-CD20 antibody rituximab reduces the T helper response. Arthr Rheumat. doi: 10.1002/art.30314. In press. [DOI] [PubMed] [Google Scholar] · DOI
  78. [84]Sutton C, Brereton C, Keogh B, Mills KH, Lavelle EC. A crucial role for interleukin (IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis. J Exp Med. 2006;203(7):1685–1691. doi: 10.1084/jem.20060285. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  79. [85]Chizzolini C, Chicheportiche R, Alvarez M, et al. Prostaglandin E2 synergistically with interleukin-23 favors human Th17 expansion. Blood. 2008;112(9):3696–3703. doi: 10.1182/blood-2008-05-155408. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  80. [86]Larsen CM, Faulenbach M, Vaag A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356(15):1517–1526. doi: 10.1056/NEJMoa065213. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  81. [87]Donath MY, Weder C, Brunner A, et al. XOMA 052, a potential disease modifying anti-1L–1beta antibody, shows sustained HbA1c reductions 3 months after a single injection with no increases in safety parameters in subjects with Type 2 diabetes. Diabetes. 2009;58:A30. [Google Scholar]
  82. [88]Carmi Y, Voronov E, Dotan S, et al. The role of macrophage-derived IL-1 in induction and maintenance of angiogenesis. J Immunol. 2009;183:4705–4714. doi: 10.4049/jimmunol.0901511. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  83. [89]Coxon A, Bolon B, Estrada J, et al. Inhibition of interleukin-1 but not tumor necrosis factor suppresses neovascularization in rat models of corneal angiogenesis and adjuvant arthritis. Arthritis Rheum. 2002;46(10):2604–2612. doi: 10.1002/art.10546. [DOI] [PubMed] [Google Scholar] · DOI
  84. [90]Voronov E, Shouval DS, Krelin Y, et al. IL-1 is required for tumor invasiveness and angiogenesis. Proc Natl Acad Sci U S A. 2003;100(5):2645–2650. doi: 10.1073/pnas.0437939100. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  85. [91]Olson JL, Courtney RJ, Rouhani B, Mandava N, Dinarello CA. Intravitreal anakinra inhibits choroidal neovascular membrane growth in a rat model. Ocul Immunol Inflamm. 2009;17(3):195–200. doi: 10.1080/09273940802710705. [DOI] [PubMed] [Google Scholar] · DOI
  86. [92]Antin JH, Weisdorf D, Neuberg D, et al. Interleukin-1 blockade does not prevent acute graft-versus-host disease: results of a randomized, double-blind, placebo-controlled trial of interleukin-1 receptor antagonist in allogeneic bone marrow transplantation. Blood. 2002;100(10):3479–3482. doi: 10.1182/blood-2002-03-0985. [DOI] [PubMed] [Google Scholar] · DOI
  87. [93]Antin JH, Weinstein HJ, Guinan EC, et al. Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease. Blood. 1994;84(4):1342–1348. [PubMed] [Google Scholar]
  88. [94]Wood DD, Ihrie EJ, Dinarello CA, Cohen PL. Isolation of an interleukin-1-like factor from human joint effusions. Arthritis Rheum. 1983;26(8):975–983. doi: 10.1002/art.1780260806. [DOI] [PubMed] [Google Scholar] · DOI
  89. [95]Duff GW, Atkins E, Malawista SE. The fever of gout: urate crystals activate endogenous pyrogen production from human and rabbit mononuclear phagocytes. Trans Assoc Am Physicians. 1983;96:234–245. [PubMed] [Google Scholar]
  90. [96]So A, De Smedt T, Revaz S, Tschopp J. A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther. 2007;9(2):R28. doi: 10.1186/ar2143. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  91. [97]Terkeltaub R. Update on gout: new therapeutic strategies and options. Nat Rev Rheumatol. 2010;6(1):30–38. doi: 10.1038/nrrheum.2009.236. [DOI] [PubMed] [Google Scholar] · DOI
  92. [98]So A, De Meulemeester M, Pikhlak A, et al. Canakinumab for the treatment of acute flares in difficult-to-treat gouty arthritis: Results of a multicenter, phase II, dose-ranging study. Arthritis Rheum. 2010;62(10):3064–3076. doi: 10.1002/art.27600. [DOI] [PubMed] [Google Scholar] · DOI
  93. [100]Joosten LA, Netea MG, Mylona E, et al. Engagement of fatty acids with Toll-like receptor 2 drives interleukin-1beta production via the ASC/caspase 1 pathway in monosodium urate monohydrate crystal-induced gouty arthritis. Arthritis Rheum. 2010;62(11):3237–3248. doi: 10.1002/art.27667. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  94. [101]Dinarello CA. How interleukin-1beta induces gouty arthritis. Arthritis Rheum. 2010;62(11):3140–3144. doi: 10.1002/art.27663. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  95. [102]Ghezzi P, Dinarello CA, Bianchi M, Rosandich ME, Repine JE, White CW. Hypoxia increases production of interleukin-1 and tumor necrosis factor by human mononuclear cells. Cytokine. 1991;3(3):189–194. doi: 10.1016/1043-4666(91)90015-6. [DOI] [PubMed] [Google Scholar] · DOI
  96. [103]Emsley HC, Smith CJ, Georgiou RF, et al. A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients. J Neurol Neurosurg Psychiatry. 2005;76(10):1366–1372. doi: 10.1136/jnnp.2004.054882. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  97. [104]Mandrup-Poulsen T, Pickersgill L, Donath MY. Blockade of interleukin 1 in type 1 diabetes mellitus. Nat Rev Endocrinol. 2010;6(3):158–166. doi: 10.1038/nrendo.2009.271. [DOI] [PubMed] [Google Scholar] · DOI
  98. [105]Maedler K, Sergeev P, Ris F, et al. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest. 2002;110(6):851–860. doi: 10.1172/JCI15318. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  99. [106]Dinarello CA, Donath MY, Mandrup-Poulsen T. Role of IL-1beta in type 2 diabetes. Curr Opin Endocrinol Diabetes Obes. 2010;17(4):314–321. doi: 10.1097/MED.0b013e32833bf6dc. [DOI] [PubMed] [Google Scholar] · DOI
  100. [108]Stienstra R, Joosten LA, Koenen T, et al. The inflammasome-mediated caspase-1 activation controls adipocyte differentiation and insulin sensitivity. Cell Metab. 2010;12(6):593–605. doi: 10.1016/j.cmet.2010.11.011. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  101. [109]Joosten LA, Smeets RL, Koenders MI, et al. Interleukin-18 promotes joint inflammation and induces interleukin-1-driven cartilage destruction. Am J Pathol. 2004;165(3):959–967. doi: 10.1016/S0002-9440(10)63357-3. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  102. [110]Chevalier X, Goupille P, Beaulieu AD, et al. Intraarticular injection of anakinra in osteoarthritis of the knee: a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2009;61(3):344–352. doi: 10.1002/art.24096. [DOI] [PubMed] [Google Scholar] · DOI
  103. [111]Abbate A, Kontos MC, Grizzard JD, et al. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction. Am J Cardiol. 2010;105(10):1371–1377. doi: 10.1016/j.amjcard.2009.12.059. [DOI] [PubMed] [Google Scholar] · DOI

Cited by

Sorted by citations

Authors
Dinarello, C. A.
Affiliations
Radboud University Nijmegen (NL)
Corresponding author
Dinarello, Charles A.
ORCID
Dinarello, Charles A.
Venue
Blood
Publisher
American Society of Hematology
Published
2011-04-07
Volume
117
Issue
14
Pages
3720-3732
ISSN
  • 0006-4971 (ISSN-L)
  • 1528-0020
DOI
10.1182/blood-2010-07-273417
PMC
PMC3083294
OpenAlex
W2150107812
Cited by
2,248
References
118
Citations by year
2026: 138 · 2025: 173 · 2024: 151 · 2023: 150 · 2022: 161 · 2021: 160 · 2020: 159 · 2019: 164 · 2018: 151 · 2017: 145 · 2016: 123 · 2015: 154 · 2014: 139 · 2013: 124 · 2012: 110
FWCI
12.05
Type
journal article
Language
en
Open access
Locations
  • Blood (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Radboud Repository (Radboud University) (submittedVersion)
Funders
  • National Cancer Institute (CA 046934, P30CA046934)
  • National Institute of Allergy and Infectious Diseases (AI‑15614, R56AI015614, R01AI015614)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
interleukin-1, IL-1 receptor family, innate immunity, autoinflammatory disease, autoimmune disease, caspase-1, gout, type 2 diabetes, rheumatoid arthritis, recurrent pericarditis, smoldering multiple myeloma, heart failure, anti-inflammatory therapy
MeSH terms
Animals, Autoimmune Diseases, Disease, Multigene Family, Humans, Inflammation, Interleukin-1, Models, Biological, Receptors, Interleukin-1, Toll-Like Receptors, Molecular Targeted Therapy

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