Skip to main content
SpringerLink
Log in

IL-1 Receptor Antagonist-Deficient Mice

  • Chapter
Book cover Cytokine Knockouts

Part of the book series: Contemporary Immunology ((CONTIM))

  • 382 Accesses

Abstract

Interleukin-1 receptor antagonist (IL-1Ra) is unique among primary inflammatory cytokines because its molecular activity is entirely passive and negative (1–3). Because it is a pure antagonist of the inflammatory cytokine IL-1, a deficiency of IL-1Ra not only reveals processes for which IL-1Ra is essential but highlights pathologies that involve overactivity of IL-1. IL-1Ra deficiency is not associated with developmental pathology. To some extent IL-1Ra knockouts resemble transgenics that overexpress inflammatory cytokines (see, for example, refs. 4 and 5) in that both types of mice develop site-specific inflammatory diseases because of localized excessive inflammatory responses. The remarkable feature of the inflammatory diseases that we observe in IL-1Ra-deficient mice is that they are tissue-specific without any intention on the part of the investigators to target the hyperactivity of IL-1. The disturbed balance of activity of the IL-1 system, even though it is part of the innate immune system, appears to feed into the activity of the adaptive immune response, creating autoimmune conditions. Investigating the mechanism for this specificity may well yield important insights into the nature of chronic inflammatory diseases.

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 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
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

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Eisenberg, S. P., Evans, R. J., Arend, W. P., et al. (1990) Primary structure and functional expression from complementary-DNA of a human interleukin-1 receptor antagonist. Nature 343, 341–346.

    Article  PubMed  CAS  Google Scholar 

  2. Hannum, C. H., Wilcox, C. J., Arend, W. P., et al. (1990) cDNA cloning of an intracellular form of the human interleukin-1 receptor antagonist associated with epithelium. Nature 343, 336–340.

    Article  PubMed  CAS  Google Scholar 

  3. Dripps, D. J., Verderber, E., Ng, R. K., Thompson, R. C., and Eisenberg, S. P. (1991) Interleukin-1 receptor antagonist binds to the type-II interleukin-1 receptor on B-cells and neutrophils. J. Biol. Chem. 266, 20311–20315.

    PubMed  CAS  Google Scholar 

  4. Kassiotis, G. and Kollias, G. (2001) TNF and receptors in organ-specific autoimmune disease: multi-layered functioning mirrored in animal models. J. Clin. Invest. 107, 1507–1508.

    Article  PubMed  CAS  Google Scholar 

  5. Niki, Y., Yamada, H., Seki, S., et al. (2001) Macrophage-and neutrophil-dominant arthritis in human IL-1 alpha transgenic mice. J. Clin. Invest. 107, 1127–1135.

    Article  PubMed  CAS  Google Scholar 

  6. Nicklin, M. J. H., Barton, J. L., Nguyen, M., FitzGerald, M. G., Duff, G. W., and Kornman, K. (2002) A sequence-based map of the nine genes of the human interleukin-1 cluster. Genomics 79, 718–725.

    Article  PubMed  CAS  Google Scholar 

  7. Taylor, S. L., Renshaw, B. R., Garka, K. E., Smith, D. E., and Sims, J. E. (2002) Genomic organization of the interleukin-1 locus. Genomics 79, 726–733.

    Article  PubMed  CAS  Google Scholar 

  8. Graves, B. J., Hatada, M. H., Hendrickson, W. A., Miller, J. K., Madison, V. S., and Satow, Y. (1990) Structure of interleukin 1-alpha at 2.7-a resolution. Biochemistry 29, 2679–2684.

    Article  PubMed  CAS  Google Scholar 

  9. Priestle, J. P., Schar, H. P., and Grutter, M. G. (1989) Crystallographic refinement of interleukin1-beta at 2.0 A resolution. Proc. Natl. Acad. Sci. USA 86, 9667–9671.

    Article  PubMed  CAS  Google Scholar 

  10. Vigers, G. P. K., Caffes, P., Evans, R. J., Thompson, R. C., Eisenberg, S. P., and Brandhuber, B. J. (1994) X-ray structure of interleukin-1 receptor antagonist at 2.0-Angstrom resolution. J. Biol. Chem. 269, 12874–12879.

    PubMed  CAS  Google Scholar 

  11. Sims, J. E., Nicklin, M. J. H., Bazan, J. F., et al. (2001) A new nomenclature for IL-1-family genes. Trends Immunol. 22, 536–537.

    Article  PubMed  CAS  Google Scholar 

  12. Dunn, E., Sims, J. E., Nicklin, M. J. H., and O’Neill, L. A. J. (2001) Annotating genes with potential roles in the immune system: six new members of the IL-1 family. Trends Immunol. 22, 533–536.

    Article  PubMed  CAS  Google Scholar 

  13. Barton, J. L., Herbst, R., Bosisio, D., Higgins, L., and Nicklin, M. J. H. (2000) A tissue specific IL-1 receptor antagonist homolog from the IL-1 cluster lacks IL-1, IL-Ira, IL-18 and IL-18 antagonist activities. Eur. J. Immunol. 30, 3299–3308.

    Article  PubMed  CAS  Google Scholar 

  14. Lin, H. S., Ho, A. S., Haley-Vicente, D., et al. (2001) Cloning and characterization of IL-1HY2, a novel interleukin-1 family member. J Biol. Chem. 276, 20597–20602.

    Article  PubMed  CAS  Google Scholar 

  15. Silver, A. R. J., Masson, W. K., George, A. M., Adam, J., and Cox, R. (1990) The IL-1-alpha-gene and IL-1-beta-gene are closely linked (less-than 70 kb) on mouse chromosome-2. Somat. Cell Mol. Genet. 16, 549–556.

    Article  PubMed  CAS  Google Scholar 

  16. Zahedi, K., Seldin, M. F., Rits, M., Ezekowitz, R. A. B., and Whitehead, A. S. (1991) Mouse IL-1 receptor antagonist protein—molecular characterization, gene-mapping, and expression of messenger-RNA in vitro and in vivo. J. Immunol. 146, 4228–4233.

    PubMed  CAS  Google Scholar 

  17. Horai, R., Asano, M., Sudo, K., et al. (1998) Production of mice deficient in genes for interleukin (IL)-1 alpha, IL-1 beta, IL-1 alpha/beta, and IL-1 receptor antagonist shows that IL-1 beta is crucial in turpentine-induced fever development and glucocorticoid secretion. J. Exp. Med. 187, 1463–1475.

    Article  PubMed  CAS  Google Scholar 

  18. Zahedi, K. A., Uhlar, C. M., Rits, M., Prada, A. E., and Whitehead, A. S. (1994) The mouse interleukin-1 receptor antagonist protein—gene structure and regulation in-vitro. Cytokine 6, 1–9.

    Article  PubMed  CAS  Google Scholar 

  19. Gabay, C., Porter, B., Fantuzzi, G., and Arend, W. P. (1997) Mouse IL-1 receptor antagonist isoforms: complementary DNA cloning and protein expression of intracellular isoform and tissue distribution of secreted and intracellular IL-1 receptor antagonist in vivo. J. Immunol. 159, 5905–5913.

    PubMed  CAS  Google Scholar 

  20. Irikura, V. M., Lagraoui, M., and Hirsh, D. (2002) The epistatic relationships between IL-1, IL-1 receptor antagonist, and the type I IL-1 receptor. J. Immunol. 169, 393–398.

    PubMed  CAS  Google Scholar 

  21. Malyak, M., Guthridge, J. M., Hance, K. R., Dower, S. K., Freed, J. H., and Arend, W. P. (1998a) Characterization of a low molecular weight isoform of IL-1 receptor antagonist. J Immunol. 161, 1997–2003.

    PubMed  CAS  Google Scholar 

  22. Haskill, S., Martin, G., Van Le, L., et al. (1991) cDNA cloning of an intracellular form of the human interleukin-1 receptor antagonist assocviated with epithelium. Proc. Natl. Acad. Sci. USA 88, 3681–3685.

    Google Scholar 

  23. Muzio, M., Polentarutti, N., Facchetti, F., et al. (1999) Characterization of type II intracellular IL-1 receptor antagonist (IL-lra3): a depot IL-lra. Eur. J. Immunol. 29, 781–788.

    Article  PubMed  CAS  Google Scholar 

  24. Seckinger, P., Williamson, K., Balavoine, J. F., et al. (1987) A urine inhibitor of interleukin-1 activity affects both interleukin 1 a and 1f3 but not tumor necrosis factor a. J. Immunol. 139, 1541–1545.

    PubMed  CAS  Google Scholar 

  25. Seckinger, P., Lowenthal, J. W., Williamson, K., Dayer, J. M., and MacDonald, H. R. (1987) A urine inhibitor of interleukin 1 activity that blocks ligand binding. J. Immunol. 139, 1546–1549.

    PubMed  CAS  Google Scholar 

  26. Greenfeder, S. A., Nunes, P., Kwee, L., Labow, M., Chizzonite, R. A., and Ju, G. (1995) Molecular cloning and characterization of a second subunit of the interleukin 1 receptor complex. J. Biol. Chem. 270, 13757–13765.

    Article  PubMed  CAS  Google Scholar 

  27. Korherr, C., Hofmeister, R., Wesche, H., and Falk, W. (1997) A critical role for interleukin-1 receptor accessory protein in interleukin-1 signaling. Eur. J. Immunol. 27, 262–267.

    Article  PubMed  CAS  Google Scholar 

  28. Schreuder, H., Tardif, C., Trump-Kallmeyer, S., et al. A new cytokine-receptor binding mode revealed by the crystal structure of the IL-1 receptor with an antagonist. Nature 386, 194–200.

    Google Scholar 

  29. Vigers, G. P. A., Anderson, L. J., Caffes, P., and Brandhuber, B. J. (1997) Crystal structure of the type-I interleukin-1 receptor complexed with interleukin-1 beta. Nature 386, 190–194.

    Article  PubMed  CAS  Google Scholar 

  30. Colotta, F., Re, F., Muzio, M., et al. (1993) Interleukin-1 type II receptor-a decoy target for IL-1 that is regulated by IL-4. Science 261, 472–475.

    Article  PubMed  CAS  Google Scholar 

  31. Malinowsky, D., Lundkvist, J., Laye, S., and Bartfai, T. (1998) Interleukin-1 receptor accessory protein interacts with the type II interleukin-1 receptor. FEBS Lett. 429, 299–302.

    Article  PubMed  CAS  Google Scholar 

  32. McMahan, C. J., Slack, J. L., Mosley, B., et al. (1991) A novel IL-1 receptor, cloned from B cells by mammalian expression, is expressed in many cell-types. EMBO J. 10, 2821–2832.

    PubMed  CAS  Google Scholar 

  33. Watson, J. M., Lofquist, A. K., Rinehart, C. A., et al. (1995) The intracellular IL-1 receptor antagonist alters IL-1-inducible gene-expression without blocking exogenous signaling by IL-113. J. Immunol. 155, 4467–4475.

    PubMed  CAS  Google Scholar 

  34. Janson, R. W., Hance, K. R., and Arend, W. P. (1991) Production of IL-1-receptor antagonist by human in vitro-derived macrophages-effects of lipopolysaccharide and granulocyte-macrophage colony-stimulating factor. J. Immunol. 147, 4218–4223.

    PubMed  CAS  Google Scholar 

  35. Lore, K., Sonnerborg, A., Spetz, A. L., Andersson, U., and Andersson, J. (1998) Immunocytochemical detection of cytokines and chemokines in Langerhans cells and in vitro derived dendritic cells. J. Immunol. Methods 214, 97–111.

    Article  PubMed  CAS  Google Scholar 

  36. McColl, S. R., Paquin, R., Menard, C., and Beaulieu, A. D. (1992) Human neutrophils produce high-levels of the interleukin-1 receptor antagonist in response to granulocyte macrophage colony-stimulating factor and tumor necrosis factor a. J. Exp. Med. 179, 593–598.

    Article  Google Scholar 

  37. Malyak, M., Smith, M. F., Abel, A. A., and Arend, W. P. (1994) Peripheral-blood neutrophil production of interleukin-1 receptor antagonist and interleukin-1(3. J. Clin. Immunol. 14, 20–30.

    Article  PubMed  CAS  Google Scholar 

  38. Dewberry, R. M., Holden, H., Crossman, D. C., and Francis, S. E. (2000) Interleukin-1 receptor antagonist expression in human endothelial cells and atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 20, 2394–2400.

    Article  PubMed  CAS  Google Scholar 

  39. Hagaman, D. D., Okayama, Y., D’Ambrosio, C., Prussin, C., Gilfillan, A. M., and Metcalfe, D. D. (2001) Secretion of interleukin-1 receptor antagonist from human mast cells after immunoglobulin E-mediated activation and after segmental antigen challenge. Am. J. Respir. Cell Mol. Biol. 25, 685–691.

    PubMed  CAS  Google Scholar 

  40. Chan, L. S., Hammerberg, C., Kang, K., Sabb, P., Tavakkol, A., and Cooper, K. D. (1992) Human dermal fibroblast interleukin-1 receptor antagonist (IL-1Ra) and interleukin- 1-beta(IL-113) messenger-RNA and protein are co-stimulated by phorbol ester—implication for a homeostatic mechanism. J. Invest. Derm. 99, 315–322.

    Article  PubMed  CAS  Google Scholar 

  41. Silvera, M. R. and Phipps, R. P. (1995) Synthesis of interleukin-1 receptor antagonist by Thy-1(+) and Thy-1(-) murine lung fibroblast subsets. J. Interferon Cytokine Res. 15, 63–70.

    Article  PubMed  CAS  Google Scholar 

  42. Steinkasserer, A., Estaller, C., Weiss, E. H., and Sim, R. B. (1992) Human interleukin-1 receptor antagonist is expressed in liver. FEBS Lett. 310, 60–62.

    Article  PubMed  CAS  Google Scholar 

  43. Gabay, C., Porter, B., Guenette, D., Billir, B., and Arend, W. P. (1999) Interleukin-4 (IL-4) and IL-13 enhance the effect of IL-1 beta on production of IL-1 receptor antagonist by human primary hepatocytes and hepatoma HepG2 cells: differential effect on C-reactive protein production. Blood 93, 1299–1307.

    PubMed  CAS  Google Scholar 

  44. Cerretti, D. P., Kozlosky, C. J., Mosley, B., et al. (1992) Molecular-cloning of the interleukin-1-beta converting enzyme. Science 256, 97–100.

    Article  PubMed  CAS  Google Scholar 

  45. MacKenzie, A., Wilson, H. L., Kiss-Toth, E., Dower, S. K., North, R. A., and Surprenant, A. (2001) Rapid secretion of interleukin-1 beta by microvesicle shedding. Immunity 15, 825–835.

    Article  PubMed  CAS  Google Scholar 

  46. Arend, W. P. and Leung, D. Y. M. (1994) IgG induction of IL-1 receptor antagonist production by human monocytes. Immunol. Rev. 139, 71–78.

    Article  PubMed  CAS  Google Scholar 

  47. Arend, W. P., Smith, M. F. Jr., Janson, R., and Joslin, F. G. (1991) IL-1 receptor antagonist and IL-1-beta production in human monocytes are regulated differently. J. Immunol. 147, 1530–1536.

    PubMed  CAS  Google Scholar 

  48. Fenton, M. J., Buras, J. A., and Donnelly, R. P. (1992) IL-4 reciprocally regulates IL-1 and IL-1 receptor antagonist expression in human monocytes. J. Immunol. 149, 1283–1288.

    PubMed  CAS  Google Scholar 

  49. Vannier, E., Miller, L. C., and Dinarello, C. (1992) Co-ordinated anti-inflammatory effects of interleukin-4. Interleukin-4 suppresses interleukin-1 production but up-regiulates gene-expression and synthesis of interleukin-1 receptor antagonist. Proc. Natl. Acad. Sci. USA 89, 4076–4080.

    Article  PubMed  CAS  Google Scholar 

  50. Beasley, D., McGuiggin, M. E., and Dinarello, C. A. (1995) Human vascular smooth-muscle cells produce an intracellular form of interleukin-1 receptor antagonist. Am. J. Physiol. 38, C961 - C968.

    Google Scholar 

  51. Bigler, C. F., Norris, D. A., Weston, W. L., and Arend, W. P. (1992) Interleukin-1 receptor antagonist production by human keratinocytes. J. Invest. Dermatol. 98, 38–44.

    Article  PubMed  CAS  Google Scholar 

  52. Levine, S. J., Wu, T., and Shelhamer, J. H. (1997) Extracellular release of the type I intracellular IL-1 receptor antagonist from human airway epithelial cells—differential effects of IL-4, IL-13, IFN-gamma, and corticosteroids. J. Immunol. 158, 5949–5957.

    PubMed  CAS  Google Scholar 

  53. Merot, Y., Didienean, L., Dayer, J. M., Fournier, C., Canaux, P., and Saurat, J. H. (1987) Immunoreactive interleukin-1 (IL-1) alpha and beta in normal human-skin. J. Invest. Dermatol. 89, 327.

    Google Scholar 

  54. Hirsch, E., Irikura, V. M., Paul, S. M., and Hirsh, D. (1996) Functions of interleukin 1 receptor antagonist in gene knockout and overproducing mice. Proc. Natl. Acad. Sci. USA 93, 11008–11013.

    Article  PubMed  CAS  Google Scholar 

  55. Nicklin, M. J. H., Hughes, D. E., Barton, J. L., Ure, J. M., and Duff, G. W. (2000) Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene. J. Exp. Med. 191, 303–311.

    Article  PubMed  CAS  Google Scholar 

  56. Hentze, M. W. and Kulozik, A. E. (1999) A perfect message: RNA surveillance and nonsense-mediated decay. Cell 96, 307–310.

    Article  PubMed  CAS  Google Scholar 

  57. Ma, Y. H., Thornton, S., Boivin, G. P., Hirsh, D., Hirsch, R., and Hirsch, E. (1998) Altered susceptibility to collagen-induced arthritis in transgenic mice with aberrant expression of interleukin-1 receptor antagonist. Arthritis Rheum. 41, 1798–1805.

    Article  PubMed  CAS  Google Scholar 

  58. Devlin, C. M., Kuriakose, G., Hirsch, E., and Tabas, I. (2002) Genetic alterations of IL-1 receptor antagonist in mice affect plasma cholesterol level and foam cell lesion size. Proc. Natl. Acad. Sci. USA 99, 6281–6285.

    Article  Google Scholar 

  59. Nagy, A., Rossant, J., Nagy, R., Abramow-Newerly, W., and Roder, J. C. (1990) Derivation of completely cell culture-derived mice from early-passage embryonic stem-cells. Proc. Natl. Acad. Sci USA 90, 8424–8428.

    Article  Google Scholar 

  60. Horai, R., Saijo, S., Tanika, M., et al. (2000) Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J. Exp. Med. 191, 313–320.

    Article  PubMed  CAS  Google Scholar 

  61. Josephs, M. D., Solorzano, C. C., Taylor, M., et al. (2000) Modulation of the acute phase response by altered expression of the IL-1 type 1 receptor or IL-lra. Am. J. Physiol. 278, R824 - R830.

    CAS  Google Scholar 

  62. Wallenius, V., Wallenius, K., Ahren, B., et al. (2002) Interleukin-6-deficient mice develop mature onset obesity. Nature Med. 8, 75–79.

    Article  PubMed  CAS  Google Scholar 

  63. Glaccum, M. B., Stocking, K. L., Charrier, K., et al. (1997) Phenotypic and functional characterization of mice that lack the type I receptor for IL-1. J. Immunol. 159, 3364–3371.

    PubMed  CAS  Google Scholar 

  64. Dinarello, C. A., Ikejima, T., Warner, S. J. C., et al. (1987) Interleukin-1 induces interleukin-1.1. Induction of circulating interleukin-1 in rabbits in vivo and in human mononuclear cells in vitro. J. Immunol. 139, 1902–1910.

    PubMed  CAS  Google Scholar 

  65. Warner, S. J. C., Auger, K. R., and Libby, P. (1987) Human interleukin-1 induces interleukin-1 gene-expression in human vascular smooth-muscle cells. J. Exp. Med. 165, 1316–1331.

    Article  PubMed  CAS  Google Scholar 

  66. Leon, L. R., Conn, C. A., Glaccum, M., and Kluger, M. J. (1996) IL-1 type I receptor mediates acute phase response to turpentine, but not lipopolysaccharide, in mice. Am. J. Physiol. 271, R1668 - R1675.

    PubMed  CAS  Google Scholar 

  67. Ross, R. (1995) Cell biology of atherosclerosis. Annu. Rev. Physiol. 57, 791–804.

    Article  PubMed  CAS  Google Scholar 

  68. Francis, S. E., Camp, N. J., Dewberry, R. M., et al. (1999) Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease. Circulation 99, 861–866.

    Article  PubMed  CAS  Google Scholar 

  69. Garcia-Cardena, G., Comander, J., Anderson, K. R., Blackman, B. R., and Gimbrone, M. A. (2001) Biomechanical activation of vascular endothelium as a determinant of its functional phenotype. Proc. Natl. Acad. Sci. USA 98, 4478–4485.

    Article  PubMed  CAS  Google Scholar 

  70. Iwakura, Y. (2002) Roles of IL-1 in the development of rheumatoid arthritis: consideration from mouse models. Cytokine Growth Factor Rev. 13, 341–355.

    Article  PubMed  CAS  Google Scholar 

  71. Simon, A. K., Seipelt, E., and Seiper, J. (1994) Divergent T cell cytokine patterns in inflammatory arthritis. Proc. Natl. Acad. Sci USA 91, 8562–8566.

    Article  PubMed  CAS  Google Scholar 

  72. Chatelain, R., Varkila, K., and Cofman, R. L. (1992) IL-4 induces a TH2 response in Leishmania major-infected mice. J. Immunol. 148, 1182–1187.

    PubMed  CAS  Google Scholar 

  73. Vollmer, S., Menssen, A., and Prinz, J. C. (1994) T lymphocytes derived from skin lesions of patients with psoriasis vulgaris express a novel cytokine pattern that is distinct from that of T helper type 1 and type 2 cells. Eur. J. Immunol. 24, 3277–3282.

    Article  Google Scholar 

  74. Schlaak, J. F., Buslau, M., Jochum, W., et al. (1994) T-cells involved in psoriasis vulgaris belong to the TH1 subset. J. Invest. Dermatol. 102, 145–149.

    Article  PubMed  CAS  Google Scholar 

  75. Uyemura, K., Yamamura, M., Fivenson, D. F., Modlin, R. L., and Nickoloff, B. J. (1993) The cytokine network in lesional and lesion-free psoriatic skin is characterized by T-helper type-1 cell-mediated response. J. Invest. Dermatol. 101, 701–705.

    Article  PubMed  CAS  Google Scholar 

  76. Sallusto, F., Cella, M., Danieli, C., and Lanzavecchia, A. (1995) Dendritic cells use macropinocytosis and the mannose receptor to concentrate macromolecules in the major histocompatability complex class II compartment: downregulation by cytokines and bacterial products. J. Exp. Med. 182, 389–400.

    Article  PubMed  CAS  Google Scholar 

  77. Roake, J. A., Rao, A. S., Morris, P. J., Larsen, C. P., Hankins, D. F., and Austyn, J. M. (1995) Dendritic cell loss from nonlymphoid tissue after systematic administration of lipopolysaccharide, tumor necrosis factor, and interleukin 1. J. Exp. Med. 181, 2237–2247.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. Martin J. H. Nicklin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joanna Shepherd
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Colorado Health Sciences Center, Denver, CO, USA

    Giamila Fantuzzi PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer Science+Business Media New York

About this chapter

Cite this chapter

Nicklin, M.J.H., Shepherd, J. (2003). IL-1 Receptor Antagonist-Deficient Mice. In: Fantuzzi, G. (eds) Cytokine Knockouts. Contemporary Immunology. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-405-4_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-59259-405-4_7

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-415-9

  • Online ISBN: 978-1-59259-405-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation