Skip to main content
SpringerLink
Log in

The Interleukin-1 Family

  • Chapter
  • First Online:
Regulation of Cytokine Gene Expression in Immunity and Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 941))

Abstract

The interleukin-1 (IL-1) family consists of several pro- or anti-inflammatory proteins, with pro-inflammatory IL-1β being its best characterized member. IL-1β is one of the most prominent mediators of inflammation resulting in fever and immune activation via binding to IL-1 receptor 1. Due to its potency, its secretion is tightly regulated. First the transcription of the biologically inactive proform is induced by TLR activation, TNF, or IL-1 receptor activation by mature IL-1α or IL-1β. For the secretion of IL-1β, inflammasome activation as second stimulus is needed. Inflammasomes are cytosolic protein complexes whose activation results in the maturation of inflammatory caspases such as caspase-1. Caspase-1 then cleaves the inactive pro-IL-1β into its mature form which is then being secreted. While IL-1α and IL-1β are considered pro-inflammatory, IL-1Ra as a naturally occurring receptor antagonist acts as an inhibitor on IL-1 receptor signaling. Further members of the IL-1 family, such as IL-18, IL-33, or IL-36, are even involved in T-helper-cell differentiation and will also be discussed in this chapter.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801.

    Article  CAS  PubMed  Google Scholar 

  2. Ali S, Mohs A, Thomas M, et al. The dual function cytokine IL-33 interacts with the transcription factor NF-kappaB to dampen NF-kappaB-stimulated gene transcription. J Immunol. 2011;187:1609–16.

    Article  CAS  PubMed  Google Scholar 

  3. Auron P, Webb AC, Rosenwasser LJ, et al. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984;81:7907–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Bulau AM, Nold MF, Li S, et al. Role of caspase-1 in nuclear translocation of IL-37, release of the cytokine, and IL-37 inhibition of innate immune responses. Proc Natl Acad Sci U S A. 2014;111:2650–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Burns K, Martinon F, Tschopp J. New insights into the mechanism of IL-1beta maturation. Curr Opin Immunol. 2003;15:26–30.

    Article  CAS  PubMed  Google Scholar 

  6. Carriere V, Roussel L, Ortega N, et al. IL-33, the IL-1-like cytokine ligand for ST2 receptor, is a chromatin-associated nuclear factor in vivo. Proc Natl Acad Sci U S A. 2007;104:282–7.

    Article  CAS  PubMed  Google Scholar 

  7. Chen CJ, Kono H, Golenbock D, et al. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med. 2007;13:851–6.

    Article  CAS  PubMed  Google Scholar 

  8. Dinarello C, Arend W, Sims J et al. IL-1 family nomenclature. Nat Immunol. 2010; 11:973.

    Google Scholar 

  9. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood. 1996;87:2095–147.

    CAS  PubMed  Google Scholar 

  10. Dinarello CA. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol. 2002;20:S1–13.

    CAS  PubMed  Google Scholar 

  11. Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009;27:519–50.

    Article  CAS  PubMed  Google Scholar 

  12. Dostert C, Petrilli V, Van Bruggen R, et al. Innate immune activation through Nalp3 inflammasome sensing of asbestos and silica. Science. 2008;320:674–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Fantuzzi G, Puren AJ, Harding MW, et al. Interleukin-18 regulation of interferon gamma production and cell proliferation as shown in interleukin-1beta-converting enzyme (caspase-1)-deficient mice. Blood. 1998;91:2118–25.

    CAS  PubMed  Google Scholar 

  14. Feldmeyer L, Keller M, Niklaus G, et al. The inflammasome mediates UVB-induced activation and secretion of interleukin-1beta by keratinocytes. Curr Biol. 2007;17:1140–5.

    Article  CAS  PubMed  Google Scholar 

  15. Feldmeyer L, Werner S, Le F, et al. Interleukin-1, inflammasomes and the skin. Eur J Cell Biol. 2010;89:638–44.

    Article  CAS  PubMed  Google Scholar 

  16. Fenton MJ. Review: transcriptional and post-transcriptional regulation of interleukin 1 gene expression. Int J Immunopharmacol. 1992;14:401–11.

    Article  CAS  PubMed  Google Scholar 

  17. Fettelschoss A, Kistowska M, Leibundgut-Landmann S, et al. Inflammasome activation and IL-1beta target IL-1alpha for secretion as opposed to surface expression. Proc Natl Acad Sci U S A. 2011;108:18055–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ghoreschi K, Laurence A, Yang X, et al. T helper 17 cell heterogeneity and pathogenicity in autoimmune disease. Trends Immunol. 2011;32:395–401.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ghoreschi K, Laurence A, Yang X, et al. Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature. 2010;467:967–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gross O, Yazdi AS, Thomas CJ, et al. Inflammasome activators induce interleukin-1alpha secretion via distinct pathways with differential requirement for the protease function of caspase-1. Immunity. 2012;36:388–400.

    Article  CAS  PubMed  Google Scholar 

  21. Guarda G, Zenger M, Yazdi AS, et al. Differential expression of NLRP3 among hematopoietic cells. J Immunol. 2011;186:2529–34.

    Article  CAS  PubMed  Google Scholar 

  22. Guo L, Huang Y, Chen X, et al. Innate immunological function of TH2 cells in vivo. Nat Immunol. 2015;16:1051–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Janeway Jr CA, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216.

    Article  CAS  PubMed  Google Scholar 

  24. Kapoor M, Martel-Pelletier J, Lajeunesse D, et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7:33–42.

    Article  CAS  PubMed  Google Scholar 

  25. Keller M, Ruegg A, Werner S, et al. Active caspase-1 is a regulator of unconventional protein secretion. Cell. 2008;132:818–31.

    Article  CAS  PubMed  Google Scholar 

  26. Kobayashi Y, Yamamoto K, Saido T, et al. Identification of calcium-activated neutral protease as a processing enzyme of human interleukin 1 alpha. Proc Natl Acad Sci U S A. 1990;87:5548–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Larsen CM, Faulenbach M, Vaag A, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med. 2007;356:1517–26.

    Article  CAS  PubMed  Google Scholar 

  28. March CJ, Mosley B, Larsen A, et al. Cloning, sequence and expression of two distinct human interleukin-1 complementary DNAs. Nature. 1985;315:641–7.

    Article  CAS  PubMed  Google Scholar 

  29. Mariathasan S, Weiss DS, Newton K, et al. Cryopyrin activates the inflammasome in response to toxins and ATP. Nature. 2006;440:228–32.

    Article  CAS  PubMed  Google Scholar 

  30. Marrakchi S, Guigue P, Renshaw BR, et al. Interleukin-36-receptor antagonist deficiency and generalized pustular psoriasis. N Engl J Med. 2011;365:620–8.

    Article  CAS  PubMed  Google Scholar 

  31. Martin MU. Special aspects of interleukin-33 and the IL-33 receptor complex. Semin Immunol. 2013;25:449–57.

    Article  CAS  PubMed  Google Scholar 

  32. Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002;10:417–26.

    Article  CAS  PubMed  Google Scholar 

  33. Martinon F, Petrilli V, Mayor A, et al. Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature. 2006;440:237–41.

    Article  CAS  PubMed  Google Scholar 

  34. Moussion C, Ortega N, Girard JP. The IL-1-like cytokine IL-33 is constitutively expressed in the nucleus of endothelial cells and epithelial cells in vivo: a novel ‘alarmin’? PLoS ONE. 2008;3, e3331.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Netea MG, Joosten LA, Lewis E, et al. Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. Nat Med. 2006;12:650–6.

    Article  CAS  PubMed  Google Scholar 

  36. Nold-Petry CA, Lo CY, Rudloff I, et al. IL-37 requires the receptors IL-18Ralpha and IL-1R8 (SIGIRR) to carry out its multifaceted anti-inflammatory program upon innate signal transduction. Nat Immunol. 2015;16:354–65.

    Article  CAS  PubMed  Google Scholar 

  37. Novick D, Kim S, Kaplanski G et al. Interleukin-18, more than a Th1 cytokine. Semin Immunol. 2013; 25:439–48.

    Google Scholar 

  38. Petrilli V, Papin S, Dostert C, et al. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 2007;14:1583–9.

    Article  CAS  PubMed  Google Scholar 

  39. Polumuri Sk, Jayakar Gg, Shirey Ka et al. Transcriptional regulation of murine IL-33 by TLR and non-TLR agonists. J Immunol. 2009; 189:50–60.

    Google Scholar 

  40. Re F, Muzio M, De Rossi M, et al. The type II “receptor” as a decoy target for interleukin 1 in polymorphonuclear leukocytes: characterization of induction by dexamethasone and ligand binding properties of the released decoy receptor. J Exp Med. 1994;179:739–43.

    Article  CAS  PubMed  Google Scholar 

  41. Schiering C, Krausgruber T, Chomka A, et al. The alarmin IL-33 promotes regulatory T-cell function in the intestine. Nature. 2014;513:564–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Schmitz J, Owyang A, Oldham E, et al. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity. 2005;23:479–90.

    Article  CAS  PubMed  Google Scholar 

  43. Schroder K, Tschopp J. The inflammasomes. Cell. 2010;140:821–32.

    Article  CAS  PubMed  Google Scholar 

  44. Thornberry NA, Bull H, Calaycay JR, et al. A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature. 1992;356:768–74.

    Article  CAS  PubMed  Google Scholar 

  45. Tortola L, Rosenwald E, Abel B, et al. Psoriasiform dermatitis is driven by IL-36-mediated DC-keratinocyte crosstalk. J Clin Invest. 2012;122:3965–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Towne JE, Renshaw BR, Douangpanya J, et al. Interleukin-36 (IL-36) ligands require processing for full agonist (IL-36alpha, IL-36beta, and IL-36gamma) or antagonist (IL-36Ra) activity. J Biol Chem. 2011;286:42594–602.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Vandanmagsar B, Youm Y, Ravussin A, et al. The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med. 2011;17:179–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Yazdi AS, Drexler SK, Tschopp J. The role of the inflammasome in nonmyeloid cells. J Clin Immunol. 2010;30:623–7.

    Article  CAS  PubMed  Google Scholar 

  49. Yazdi AS, Guarda G, Riteau N, et al. Nanoparticles activate the NLR pyrin domain containing 3 (Nlrp3) inflammasome and cause pulmonary inflammation through release of IL-1alpha and IL-1beta. Proc Natl Acad Sci U S A. 2010;107:19449–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Zheng Y, Humphry M, Maguire Jj et al. Intracellular interleukin-1 receptor 2 binding prevents cleavage and activity of interleukin-1alpha, controlling necrosis-induced sterile inflammation. Immunity. 2013; 38:285–95.

    Google Scholar 

  51. Zhou R, Tardivel A, Thorens B, et al. Thioredoxin-interacting protein links oxidative stress to inflammasome activation. Nat Immunol. 2010;11:136–40.

    Article  CAS  PubMed  Google Scholar 

  52. Zhou R, Yazdi AS, Menu P, et al. A role for mitochondria in NLRP3 inflammasome activation. Nature. 2011;469:221–5.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

KG and ASY are supported by the Deutsche Forschungsgemeinschaft (DFG) SFB685 and SFB/TRR 156 to KG and ASY.

Author information

Authors and Affiliations

  1. Department of Dermatology, University of Tuebingen, Liebermeisterstr. 25, 72076, Tuebingen, Germany

    Amir S. Yazdi & Kamran Ghoreschi

Authors
  1. Amir S. Yazdi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kamran Ghoreschi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amir S. Yazdi .

Editor information

Editors and Affiliations

  1. State Key Laboratory of Microbial Metabolism, Sheng Yushou Center of Cell Biology and Immunology, School of Life Science and Biotechnology, Shanghai Jiaotong University, Shanghai, China

    Xiaojing Ma

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Yazdi, A.S., Ghoreschi, K. (2016). The Interleukin-1 Family. In: Ma, X. (eds) Regulation of Cytokine Gene Expression in Immunity and Diseases. Advances in Experimental Medicine and Biology, vol 941. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0921-5_2

Download citation

Publish with us

Policies and ethics

Search

Navigation