Journal of Clinical Immunology

, Volume 19, Issue 1, pp 1–11 | Cite as

Interleukin-18 and Interleukin-1β: Two Cytokine Substrates for ICE (Caspase-1)

  • Giamila Fantuzzi
  • Charles A. Dinarello
Article

Abstract

This special article deals with the role of processing enzymes in the generation of bioactive cytokines, particularly IL-1β and the novel cytokine IL-18, which was formerly called IFNγ-inducing factor (IGIF). The “classical” pathways of cytokine processing are described, as well as the importance of alternative cleavage enzymes. The topic of this review also concerns the biology of IL-18. The regulation of IL-18 production, the IL-18 receptor complex, and the biological effects of this novel cytokine are described.

Cytokines processing enzymes proteinase-3 interleukin-18 interleukin-1 caspases 

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REFERENCES

  1. 1.
    Dinarello CA: Biologic basis for interleukin-1 in disease. Blood 87:2095–2147, 1996Google Scholar
  2. 2.
    Zhang Y, Center DM, Wu DMH, Cruikshank WW, Yuan J, Andrews DW, Kornfeld H: Processing and activation of prointerleukin-16 by caspase-3. J Biol Chem 273:1144–1149, 1998Google Scholar
  3. 3.
    Gu Y, Kuida K, Tsutsui H, Ku G, Hsiao K, Fleming MA, Hayashi N, Higashino K, Okamura H, Nakanishi K, Kurimoto M, Tanimoto T, Flavell RA, Sato V, Harding MW, Livingston DL, Su MS-S: Activation of interferon-γ inducing factor mediated by interleukin-1β converting enzyme. Science 275:206–209, 1997Google Scholar
  4. 4.
    Clark-Lewis I, Schumacher C, Baggiolini M, Moser B: J Biol Chem 266:23128–23134, 1991Google Scholar
  5. 5.
    Thornberry NA, Bull HG, Calaycay JR, Chapman KT, Howard AD, Kostura MJ, Miller DK, Molineaux SM, Weidner JR, Aunins J, Schmidt JA, Tocci M: A novel heterodimeric cysteine protease is required for interleukin-1 beta processing in monocytes. Nature 356:768–774, 1992Google Scholar
  6. 6.
    Howard AD, Kostura MJ, Thornberry N, Ding GJF, Limjuco G, Weidner J, Salley JP, Hogquist KA, Chaplin DD, Mumford RA, Schmidt JA, Tocci MJ: IL-1-converting enzyme requires aspartic acid residues for processing of the IL-1β precursor at two distinct sites and does not cleave 31-kDa IL-1α. J Immunol 147:2964–2969, 1991Google Scholar
  7. 7.
    Ghayur T, Banerjee S, Hugunin M, Butler D, Herzog L, Carter A, Quintal L, Sekut L, Talanian R, Paskind M, Wong W, Kamen R, Tracey D, Allen H: Caspase-1 processes IFN-gamma-inducing factor and regulates LPS-induced IFN-gamma production. Nature 386:619–623, 1997Google Scholar
  8. 8.
    Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley KA, Gerhart M, Davis R, Fitzner JN, Johnson RS, Paxton RJ, March CJ, Cerretti DP: A metallo-proteinase disintegrin that releases tumour necrosis factor-α from cells. Nature 385:729–733, 1997Google Scholar
  9. 9.
    Moss ML, Jin CS-L, Milla ME, Burkhart W, Carter HL, Chen W-J, Clay WC, Didsbury JR, Hassler D, Hoffman C, Kost TA, Lambert MH, Leesnitzer A, McCauley P, McGeehan G, Mitchell J, Moyers M, Pahel G, Rocque W, Overton LK, Schoenen F, Seaton T, Su J-L, Warner J, Willard D, Becherer JD: Cloning of a disintegrin metalloproteinase that processes precursor tumournecrosis factor-α. Nature 385:733–736, 1997Google Scholar
  10. 10.
    Wilson KP, Black JA, Thomson JA, Kim EE, Griffith JP, Navia MA, Murcko MA, Chambers SP, Aldape RA, Raybuck SA, Livingston DJ: Structure and mechanism of interleukin-1β converting enzyme. Nature 370:270–275, 1994Google Scholar
  11. 11.
    Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW, Yuan J: Human ICE/CED-3 protease nomenclature. Cell 87:123, 1996Google Scholar
  12. 12.
    Walker NP, Talanian RV, Brady KD, Dang LC, Bump NJ, Ferenz CR, Franklin S, Ghayur T, Hackett MC, Hammill LD: Crystal structure of the cysteine protease interleukin-1 beta-converting enzyme: A (p20/p10)2 homodimer. Cell 78:343–352, 1994Google Scholar
  13. 13.
    Puren AJ, Fantuzzi G, Dinarello CA: Gene expression, synthesis and secretion of IL-1β and IL-18 are differentially regulated in human blood mononuclear cells and mouse spleen cells. Eur Cytokine Netw 9(abstract), 1998Google Scholar
  14. 14.
    Akita K, Ohtsuki T, Nukada Y, Tanimoto T, Namba M, Okura T, Takakura-Yamamoto R, Torigoe K, Gu Y, Su MS-S, Fuji M, Satoh-Itoh M, Yamamoto K, Kohno K, Ikeda M, Kurimoto M: Involvement of caspase-1 and caspase-3 in the production and processing of mature human interleukin-18 in monocytic THP. 1 cells. J Biol Chem 272:26595–26606, 1997Google Scholar
  15. 15.
    Li J, Billiar TR, Talanian RV, Kim YM: Nitric oxide inhibits seven members of the caspase family via S-nitrosylation. Biochem Biophys Res Commun 240:419–422, 1997Google Scholar
  16. 16.
    Dimmeler S, Haendeler J, Nehls M, Zeiher AM: Suppression of apoptosis by nitric oxide via inhibition of interleukin-1β-converting enzyme (ICE)-like and cysteine protease protein (CPP)-32-like proteases. J Exp Med 185:601–606, 1997Google Scholar
  17. 17.
    Kim Y-M, Talanian RV, Li J, Billiar TR: Nitric oxide prevents IL-1β and IFN-γ-inducing factor (IL-18) release from macrophages by inhibiting caspase-1 (IL-1β-converting enzyme). J Immunol 161:4122–4128, 1998Google Scholar
  18. 18.
    Li P, Allen H, Banerjee S, Franklin S, Herzog L, Johnston C, McDowell J, Paskind M, Rodman L, Salfeld J, Towne E, Tracey D, Wardwell S, Wei F-Y, Wong W, Kamen R, Seshadri T: Mice deficient in interleukin-1 converting enzyme (ICE) are defective in production of mature interleukin-1β and resistant to endotoxic shock. Cell 80:401–411, 1995Google Scholar
  19. 19.
    Kuida K, Lippke JA, Ku G, Harding MW, Livingston DJ, Su MS-S, Flavell RA: Altered cytokine export and apoptosis in mice deficient in interleukin-1β converting enzyme. Science 267:2000–2003, 1995Google Scholar
  20. 20.
    Fantuzzi G, Zheng H, Faggioni R, Benigni F, Ghezzi P, Sipe JD, Shaw AR, Dinarello CA: Effect of endotoxin in IL-1β-deficient mice. J Immunol 157:291–296, 1996Google Scholar
  21. 21.
    Fantuzzi G, Puren AJ, Harding MW, Livingston DJ, Dinarello CA: Interleukin-18 regulation of interferon γ production and cell proliferation as shown in interleukin-1β-converting enzyme (caspase-1)-deficient mice. Blood 91:2118–2125, 1998Google Scholar
  22. 22.
    Thronberry NA, Lazebnik Y: Caspases: Enemies within. Science 281:1312–1316, 1998Google Scholar
  23. 23.
    Black RA, Kronheim SR, Cantrell M, Deeley MC, March CJ, Prickett KS, Wignall J, Conlon PJ, Cosman D, Hopp TP: Generation of biologically active interleukin-1 beta by proteolytic cleavage of the inactive precursor. J Biol Chem 263:9437–9442, 1988Google Scholar
  24. 24.
    Dinarello CA, Cannon JG, Mier JW, Bernheim HA, LoPreste G, Lynn DL, Love RN, Webb AC, Auron PE, Reuben RC, Rich A, Wolff SM, Putney SD: Multiple biological activities of human recombinant interleukin 1. J Clin Invest 77:1734–1739, 1986Google Scholar
  25. 25.
    Hazuda DJ, Strickler J, Kueppers F, Simon PL, Young PR: Processing of precursor interleukin-1 beta and inflammatory disease. J Biol Chem 265:6318–6322, 1990Google Scholar
  26. 26.
    Irmler M, Hertig S, MacDonald HR, Sadoul R, Becherer JD, Proudfoot A, Solari R, Tschopp J: Granzyme A is an interleukin-1β-converting enzyme. J Exp Med 181:1917–1922, 1995Google Scholar
  27. 27.
    Knudsen PJ, Dinarello CA, Strom TB: Purification and characterization of a unique human interleukin 1 from the tumor cell line U937. J Immunol 136:3311–3316, 1986Google Scholar
  28. 28.
    Mizutani H, Schechter N, Lazarus G, Black RA, Kupper TS: Rapid and specific conversion of precursor interleukin 1β (IL-1β) to an active IL-1 species by human mast cells chymase. J Exp Med 174:821–825, 1991Google Scholar
  29. 29.
    Schoenbeck U, Mach F, Libby P: Generation of biologically active IL-1β by matrix metalloproteinases: A novel caspase-1-independent pathway of IL-1β processing. J Immunol 161:3340–3346, 1998Google Scholar
  30. 30.
    Beuscher HU, Guenther C, Roellinghoff M: IL-1β is secreted by activated murine macrophages as biologically inactive precursor. J Immunol 144:2179–2183, 1990Google Scholar
  31. 31.
    Hazuda DJ, Lee JC, Young PR: The kinetics of interleukin 1 secretion from activated monocytes. Differences between interleukin 1 alpha and interleukin 1 beta. J Biol Chem 263:8473–8479, 1988Google Scholar
  32. 32.
    Robache-Gallea S, Morand S, Bruneau JM, Schoot B, Tagat E, Realo E, Chouaib S, Roman-Roman S: In vitro processing of human tumor necrosis factor-α. J Biol Chem 270:23688–23692, 1995Google Scholar
  33. 33.
    Nakamura K, Komiya M: Proteolysis of human tumor necrosis factor (TNF) by endo-and exopeptidases: process of proteolysis and formation of active fragments. Biol Pharm Bull 19:672–677, 1996Google Scholar
  34. 34.
    Padrines M, Wolf M, Walz A, Baggiolini M: Interleukin-8 processing by neutrophil elastase, cathepsin G and proteinase-3. FEBS Lett 352:231–235, 1994Google Scholar
  35. 35.
    Leavell KJ, Peterson MW, Gross TJ: Human neutrophil elastase abolishes interleukin-8 chemotactic activity. J Leukoc Biol 61:361–366, 1997Google Scholar
  36. 36.
    Kekow J, Csernok E, Szymkowiak C, Gross WL: Interaction of transforming growth factor beta (TGF beta) with proteinase 3. Adv Exp Med Biol 421:307–313, 1997Google Scholar
  37. 37.
    Longley BJ, Tyrrell L, Ma Y, Williams DA, Halaban R, Langley K, Lu HS, Schehter NM: Chymase clavage of stem cell factor yields a bioactive, soluble product. Proc Natl Acad Sci USA 94:9017–9021, 1997Google Scholar
  38. 38.
    Duval-Jobe C, Leeson M, Rawitch A, Parmely MJ: Mechanism by which U937 promonocytic cells inactivate human interferongamma. J Interferon Cytokine Res 15:557–567, 1995Google Scholar
  39. 39.
    Ku G, Faust T, Lauffer LL, Livingtson DJ, Harding MW: Interleukin-1β converting enzyme inhibition blocks progression of type II collagen-induced arthritis in mice. Cytokine 8:377–386, 1996Google Scholar
  40. 40.
    Norman J, Yang J, Fink G, Carter G, Ku G, Denham W, Livingston D: Severity and mortality of experimental pancreatitis are dependent on interleukin-1 converting enzyme (ICE). J Interferon Cytokine Res 17:113–118, 1997Google Scholar
  41. 41.
    Zheng H, Fletcher D, Kozak W, Jiang M, Hofmann K, Conn CC, Siszynski D, Grabiec C, Trumbauer MA, Shaw AR, Kostura MJ, Stevens K, Rosen H, North RJ, Chen HY, Tocci MJ, Kluger MJ, Van der Ploeg LHT: Resistance to fever induction and impaired acute-phase response in interleukin-1β deficient mice. Immunity 3:9–19, 1995Google Scholar
  42. 42.
    Fantuzzi G, Dinarello CA: The inflammatory response in interleukin-1β-deficient mice: Comparison with other cytokine-related knock-out mice. J Leukoc Biol 59:489–493, 1996Google Scholar
  43. 43.
    Spector WG, Willoughby DA: The demonstration of the role of mediators in turpentine pleurisy in rats by experimental suppression of the inflammatory changes. J Pathol Bacteriol 77:1–17, 1959Google Scholar
  44. 44.
    Mariano M, Araujo VC: Relation between diaphragmatic mast-cell activity and exudate formation in acute experimental pleurisy. J Pathol 104:275–281, 1971Google Scholar
  45. 45.
    Williams DM, Johnson NW: Early colonisation of a local inflammatory lesion and its relationship to changes in systemic leucocyte availability: A study of turpentine-induced lesions in the rat. J Pathol 125:139–149, 1978Google Scholar
  46. 46.
    Fantuzzi G, Ku G, Harding MW, Livingston DL, Sipe JD, Kuida K, Flavell RA, Dinarello CA: Response to local inflammation of IL-1β converting enzyme-deficient mice. J Immunol 158:1818–1824, 1997Google Scholar
  47. 47.
    Nylander Lundqvist E, Egelrud T: Biologically active, alternatively processed interleukin-1b in psoriatic scales. Eur J Immunol 27:2165–2171, 1997Google Scholar
  48. 48.
    Nylander-Lundqvist E, Egelrud T: Formation of active IL-1 beta from pro-IL-1 beta catalyzed by stratum corneum chymotryptic enzyme in vitro. Acta Derm Venereol 77:203–206, 1997Google Scholar
  49. 49.
    Murakami K, Kobayashi F, Ikegawa R, Koyama M, Shintani N, Yoshida T, Nakamura N, Kondo T: A metalloproteinase inhibitor prevents hepatic injury in endotoxemic mice. Eur J Pharmacol 341:105–110, 1998Google Scholar
  50. 50.
    Solorzano CC, Ksontini R, Pruitt JH, Auffenberg T, Tannahill C, Galardy RE, Schultz GP, MacKay SL, Copeland EMr, Moldawer LL: A matrix metalloproteinase inhibitor prevents processing of tumor necrosis factor alpha (TNF alpha) and abrogates endotoxin-induced lethality. Shock 7:427–431, 1997Google Scholar
  51. 51.
    Liedtke W, Cannella B, Mazzaccaro RJ, Clements JM, Miller KM, Wucherpfennig KW, Gearing AJ, Raine CS: Effective treatment of models of multiple sclerosis by matrix metalloproteinase inhibitors. Ann Neurol 44:35–46, 1998Google Scholar
  52. 52.
    Niehorster M, Tiegs G, Schade UF, Wendel A: In vivo evidence for protease-catalysed mechanisms providing bioactive tumor necrosis factor α. Biochem Pharmacol 40:1601–1603, 1990Google Scholar
  53. 53.
    Scuderi P, Dorr RT, Liddil JD, Finley PR, Meltzer P, Raitano AB, Rybski J: Alpha-globulins suppress human leukocyte tumor necrosis factor secretion. Eur J Immunol 19:939–942, 1989Google Scholar
  54. 54.
    Fantuzzi G, Karasek JA, Reznikov LL, Puren AJ, Cheronis J, Dinarello CA: A role for neutrophil proteinase-3 (PR-3) in the generation of active IL-18. Eur Cytokine Netw 9(abstract), 1998Google Scholar
  55. 55.
    Campanelli D, Melchior M, Fu Y, Nakata M, Shuman H, Nathan C, Gabay JE: Cloning of cDNA for proteinase 3: A serine protease, antibiotic, and autoantigen from human neutrophils. J Exp Med 172:1709–1715, 1990Google Scholar
  56. 56.
    Mayet W-J, Csernok E, Szymkowiak C, Gross WL, Meyer zum Buschenfelde K-K: Human endothelial cells express proteinase 3, the target antigen of anticytoplasmic antibodies in Wegener's granulomatosis. Blood 82:1221–1229, 1993Google Scholar
  57. 57.
    Csernok E, Ludemann J, Gross WL, Bainton DF: Ultrastructural localization of proteinase 3, the target antigen of anti-cytoplasmic antibodies circulating in Wegener's granulomatosis. Am J Pathol 137:1113–1120, 1990Google Scholar
  58. 58.
    Braun MG, Csernok E, Gross WL, Muller-Hermelink HK: Proteinase-3, the target antigen of anticytoplasmic antibodies circulating in Wegener's granulomatosis. Immunolocalization in normal and pathological tissues. Am J Pathol 139:831–838, 1991Google Scholar
  59. 59.
    Bergenfeldt M, Axelsson L, Ohlsson K: Release of neutrophil proteinase 4 (3) and leukocyte elastase during phagocytosis and their interaction with proteinase inhibitors. Scand J Clin Lab Invest 52:823–829, 1992Google Scholar
  60. 60.
    Ralston DR, Marsh CB, Lowe MP, Wevers MD: Antineutrophil cytoplasmic antibodies induce monocyte IL-8 release. Role of surface proteinase-3, α1-antitrypsin, and Fcγ receptors. J Clin Invest 100:1416–1424, 1997Google Scholar
  61. 61.
    Csernok E, Ernst M, Schmitt W, Bainton DF, Gross WL: Activated neutrophils express proteinase 3 on their plasma membrane in vitro and in vivo. Clin Exp Immunol 95:244–250, 1994Google Scholar
  62. 62.
    Baslund B, Petersen J, Permin H, Wiik A, Wieslander J: Measurement of proteinase 3 and its complexes with alpha 1-proteinase inhibitor and anti-neutrophil cytoplasm antibodies (ANCA) in plasma. J Immunol Methods 175:215–225, 1994Google Scholar
  63. 63.
    Henshaw TJ, Malone CC, Gabay JE, Williams RCJ: Elevations of neutrophil proteinase 3 in serum of patients with Wegener's granulomatosis and polyarteritis nodosa. Arthr Rheum 37:104–112, 1994Google Scholar
  64. 64.
    Dolman KM, van de Wiel BA, Kam C-M, Abbink JJ, Hack CE, Sonnenberg A, Powers JC, von dem Borne AEGK, Goldschmeding R: Determination of proteinase-3-α1-antitrypsin complexes in inflammatory fluids. FEBS Lett 314:117–121, 1992Google Scholar
  65. 65.
    Lundberg E, Bergenfeldt M, Ohlsson K: Release of immunoreactive neutrophil proteinase 4, normally and in peritonitis. Scand J Clin Lab Invest 51:23–29, 1991Google Scholar
  66. 66.
    Jonsson P: Cardiopulmonary bypass causes release of leukocyte proteinase-3. Scand J Clin Lab Invest 56:721–723, 1996Google Scholar
  67. 67.
    Elneihoum AM, Falke P, Axelsson L, Lundberg BS, Lindgarde F, Ohlsson K: Leukocyte activation detected by increased plasma levels of inflammatory mediators in patients with ischemic cerebrovascular diseases. Stroke 27:1734–1738, 1996Google Scholar
  68. 68.
    Regelmann WE, Herron J, Seifferman C, Gray B, Elliott GR, Clawson CC: Increased sputum peroxidase activity is associated with increased pulmonary disease in cystic fibrosis. Am Rev Respir Dis 139:A70, 1989 (abstract)Google Scholar
  69. 69.
    Okamura H, Tsutsui H, Komatsu T, Yutsudo M, Hakura A, Tanimoto T, Torigoe K, Okura T, Nukada Y, Hattori K, Akita K, Namba M, Tanabe F, Konishi K, Fukuda S, Kurimoto M: Cloning of a new cytokine that induces interferon-γ. Nature 378:88–91, 1995Google Scholar
  70. 70.
    Tsutsui H, Nakanishi K, Matsui K, Higashino K, Okamura H, Miyazawa Y, Kaneda K: IFN-γ-inducing factor up-regulates Fas ligand-mediated cytotoxic activity of murine natural killer cell clones. J Immunol 157:3967–3973, 1996Google Scholar
  71. 71.
    Mileno MD, Margolis NH, Clark BD, Dinarello CA, Burke JF, Gelfand JA: Coagulation of whole blood stimulates interleukin-1β gene expression: Absence of gene transcripts in anticoagulated blood. J Infect Dis 172:308–311, 1995Google Scholar
  72. 72.
    Shapiro L, Dinarello CA: Cytokine expression during osmotic stress. Exp Cell Res 231:354–362, 1997Google Scholar
  73. 73.
    Tone M, Thompson SAJ, Tone Y, Fairchild PJ, Waldmann H: Regulation of IL-18 (IFN-γ-inducing factor) gene expression. J Immunol 159:6156–6163, 1997Google Scholar
  74. 74.
    Chupp GL, Wright EA, Wu D, Vallen-Mashikian M, Cruikshank WW, Center DM, Kornfeld H, Berman JS: Tissue and T cell distribution of precursor and mature IL-16. J Immunol 161:3114–3119, 1998Google Scholar
  75. 75.
    Stoll S, Mueller G, Kurimoto M, Saloga J, Tanimoto T, Yamauchi H, Okamura H, Knop J, Enk AH: Production of IL-18 (IFN-γ-inducing factor) messenger RNA and functional protein by murine keratinocytes. J Immunol 159:298–302, 1997Google Scholar
  76. 76.
    Xu B, Aoyama K, Yu S, Kitani A, Okamura H, Kurimoto M, Matsuyama T, Matsushita T: Expression of interleukin-18 in murine contact hypersensitivity. J Interferon Cytokine Res 18:653–659, 1998Google Scholar
  77. 77.
    Conti B, Jeong JW, Tinti C, Son JH, Joh TH: Induction of IFN-γ-inducing factor in the adrenal cortex. J Biol Chem 272:2035–2037, 1997Google Scholar
  78. 78.
    Udagawa N, Horwood NJ, Elliot J, Mackay A, Owens J, Okamura H, Kurimoto M, Chambers TJ, Gillespie MT: Interleukin-18 is produced by osteoblasts and acts via granulocyte macrophage colony-stimulating factor and not via interferon-γ to inhibit osteoclast formation. J Exp Med 185:1005–1012, 1997Google Scholar
  79. 79.
    Martin TJ, Romas E, Gillespie MT: Interleukins in the control of osteoclast differentiation. Crit Rev Eukaryot Gene Expr 8:107–123, 1998Google Scholar
  80. 80.
    Torigoe K, Ushio S, Okura T, Kobayashi S, Taniai M, Kunikate T, Murakami T, Sanou O, Kojima H, Fuji M, Ohta T, Ikeda M, Ikegami H, Kurimoto M: Purification and characterization of the human interleukin-18 receptor. J Biol Chem 272:25737–25742, 1997Google Scholar
  81. 81.
    Parnet P, Garka KE, Bonnert TP, Dower SK, Sims JE: IL-1Rrp is a novel receptor-like molecule similar to the type I interleukin-1 receptor and its homologues T1/ST2 and IL-1R AcP. J Biol Chem 271:3967–3970, 1996Google Scholar
  82. 82.
    Yoshimoto T, Takeda K, Tanaka T, Ohkusu K, Kashiwamura S, Okamura H, Akira S, Nakanishi K: IL-12 upregulates IL-18 receptor expression on T cells, Th1 cells and B cells: Synergism with IL-18 for IFNγ production. J Immunol 161:3400–3407, 1998Google Scholar
  83. 83.
    Born TL, Thomassen E, Bird TA, Sims JE: Cloning of a novel receptor subunit, AcPL, required for interleukin-18 signaling. J Biol Chem 273:29445–29450, 1998Google Scholar
  84. 84.
    Novick D, Kim S-H, Fantuzzi G, Reznikov L, Dinarello CA, Rubinstein M: A circulating IL-18 binding protein: Isolation and characterization. Eur Cytokine Netw 9(abstract), 1998Google Scholar
  85. 85.
    Kim S-H, Novick D, Fantuzzi G, Reznikov L, Dinarello CA, Rubinstein M: The interleukin-18 binding protein is a decoy receptor lacking a transmembrane domain. Eur Cytokine Netw 9(abstract), 1998Google Scholar
  86. 86.
    Rubinstein M, Novick D, Kim S-H, Fantuzzi G, Reznikov L, Dinarello CA: A family of poxvirus-encoded homologues of the interleukin-18 binding protein. Eur Cytokine Netw 9(abstract), 1998Google Scholar
  87. 87.
    Greenfeder SA, Nunes P, Kwee L, Labow M, Chizzonite RA, Ju G: Molecular cloning and characterization of a second subunit of the interleukin-1 receptor complex. J Biol Chem 270:13757–13765, 1995Google Scholar
  88. 88.
    Croston GE, Cao Z, Goeddel DV: NFkB activation by interleukin-1 requires and IL-1 receptor-associated protein kinase activity. J Biol Chem 270:16514–16517, 1995Google Scholar
  89. 89.
    Martin MU, Falk W: The interleukin-1 receptor complex and interleukin-1 signal transduction. Eur Cytokine Netw 8:5–17, 1997Google Scholar
  90. 90.
    O'Neill LAJ, Greene C: Signal transduction pathways activated by the IL-1 receptor family: Ancient signaling machinery in mammals, insects, and plants. J Leukoc Biol 63:650–657, 1998Google Scholar
  91. 91.
    Wesche H, Korherr C, Kracht M, Falk W, Resch K, Martin MU: The interleukin-1 receptor accessory protein is essential for IL-1-induced activation of interleukin-1 receptor-associated kinase (IRAK) and stress-activated protein kinases (SAP kinases). J Biol Chem 272:7727–7731, 1997Google Scholar
  92. 92.
    Huang J, Gao X, Li S, Cao Z: Recruitment of IRAK to the interleukin 1 receptor complex requires interleukin 1 receptor accessory protein. Proc Natl Acad Sci USA 94:12829–12832, 1997Google Scholar
  93. 93.
    Cao Z: Signal transduction of interleukin-1. Cytokine, 1998 (in press)Google Scholar
  94. 94.
    Cao Z, Xiong J, Takeuchi M, Kurama T, Goeddel DV: IRAK TRAF-6. Nature 383:443–446, 1996Google Scholar
  95. 95.
    Malinin NL, Boldin MP, Kovalenko AV, Wallach D: MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1. Nature 385:540–544, 1997Google Scholar
  96. 96.
    DiDonato JA, Hayakawa M, Rothwarf DM, Zandi E, Karin M: A cytokine-responsive I kappaB kinase that activates the transcription factor NF-kappaB. Nature 388:548–554, 1997Google Scholar
  97. 97.
    Kojima H, Takeuchi M, Ohta T, Nishida Y, Arai N, Ikeda M, Ikegami H, Kurimoto M: Interleukin-18 activates the IRAK-TRAF6 pathway in mouse EL-4 cells. Biochem Biophys Res Commun 244:183–186, 1998Google Scholar
  98. 98.
    Robinson D, Shibuya K, Mui A, Zonin F, Murphy E, Sana T, Hartley SB, Menon S, Kastelein R, Bazan F, O'Garra A: IGIF does not drive Th1 development but synergizes with IL-12 for interferon-γ production and activates IRAK and NFκB. Immunity 7:571–581, 1997Google Scholar
  99. 99.
    Adachi O, Kawai T, Takeda K, Matsumoto M, Tsutsui H, Sakagami M, Nakanishi K, Akira S: Targeted disruption of the MyD88 gene results in loss of IL-1-and IL-18-mediated function. Immunity 9:143–150, 1998Google Scholar
  100. 100.
    Shapiro L, Puren AJ, Barton HA, Novick D, Peskind RL, Su MS-S, Gu Y, Dinarello CA: Interleukin-18 stimulates HIV type 1 in monocytic cells. Proc Natl Acad Sci USA 95:12550–12555, 1998Google Scholar
  101. 101.
    Tsuji-Takayama K, Matsumoto S, Koide K, Takeuchi M, Ikedo M, Ohta T, Kurimoto M: Interleukin-18 induces activation and association of p56lck and MAPK in a murine TH1 clone. Biochem Biophys Res Commun 237:126–130, 1997Google Scholar
  102. 102.
    Trinchieri G: Interleukin-12: A proinflammatory cytokine with immuno-regulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol 13:251–274, 1995Google Scholar
  103. 103.
    Takeda K, Tsutsui H, Yoshimoto T, Adachi O, Yoshida N, Kishimoto K, Okamura H, Nakanishi K, Akira S: Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity 8:383–390, 1998Google Scholar
  104. 104.
    Barbulescu K, Becker C, Schlaak JF, Schmitt E, Meyer zum Büschenfelde K-H, Neurath MF: IL-12 and IL-18 differentially regulate the transcriptional activity of the human IFN-γ promotor in primary CD4+ T lymphocytes. J Immunol 160, 1998Google Scholar
  105. 105.
    Munder M, Mallo M, Eichmann K, Modolell M: Murine macrophages secrete interferon gamma upon combined stimulation with interleukin (IL)-12 and IL-18: A novel pathway of autocrine macrophage activation. J Exp Med 187:2103–2108, 1998Google Scholar
  106. 106.
    Gu Y, Wu J, Faucheu C, Lalanne J-L, Diu A, Livingston DL, Su MS-S: Interleukin-1β converting enzyme requires oligomerization for activity of processed forms in vivo. EMBO J 14:1923–1931, 1995Google Scholar
  107. 107.
    Kohno K, Kataoka J, Ohtsuki T, Suemoto Y, Okamoto I, Usui M, Ikeda M, Kurimoto M: IFN-γ-inducing factor (IGIF) is a costimulatory factor on the activation of Th1 but not Th2 cells and exerts its effect independently of IL-12. J Immunol 158:1541–1550, 1997Google Scholar
  108. 108.
    Puren AJ, Fantuzzi G, Gu Y, Su MS-S, Dinarello CA: Interleukin-18 (IFN-γ-inducing factor) induces IL-1β and IL-8 via TNFα production from non-CD14+ human blood mononuclear cells. J Clin Invest 101:711–724, 1998Google Scholar
  109. 109.
    Matsimoto S, Tsuji-Takayama K, Aizawa Y, Koide K, Takeuchi M, Ohta T, Kurimoto M: Interleukin-18 activates NFkB in murine T helper type I cells. Biochem Biophys Res Commun 234:454–457, 1997Google Scholar
  110. 110.
    Netea MG, Kulberg BJ, Amiot F, van der Meer JWM: Preferential production of interleukin-6 and IL-1β by murine peritoneal macrophages exposed to IL-18: No role for TNF and lymphotoxin-α. Eur Cytokine Netw 9(abstract). 1998Google Scholar
  111. 111.
    Ushio S, Namba M, Okura T, Hattori K, Nukada Y, Akita K, Tanabe F, Konishi K, Mcallef M, Fujii M, Torigoe K, Tanimoto T, Fukuda S, Ikeda M, Okamura H, Kurimoto M: Cloning of the cDNA for human IFN-γ-inducing factor, expression in Escherichia coli, and studies on the biologic activities of the protein. J Immunol 156:4274–4279, 1996Google Scholar
  112. 112.
    Micallef MJ, Ohtsuki T, Kohno K, Tanabe F, Ushio S, Namba M, Tanimoto T, Torigoe K, Fujii M, Ikeda M, Fukuda S, Kurimoto M: Interferon-γ-inducing factor enhances T helper 1 cytokine production by stimulated human T cells: synergism with interleukin-12 for interferon-γ production. Eur J Immunol 26:1647–1651, 1996Google Scholar
  113. 113.
    Okamura H, Nagata K, Komatsu T, Tanimoto T, Nukata Y, Tanabe F, Akita K, Torigoe K, Okura T, Fukuda S, Kurimoto M: A novel costimulatory factor for gamma interferon induction found in the livers of mice causes endotoxic shock. Infect Immun 63:3966–3972, 1995Google Scholar
  114. 114.
    Yoshimoto T, Okamura H, Tagawa Y-I, Iwakura Y, Nakanishi K: Interleukin-18 together with interleukin-12 inhibits IgE production by induction of interferon-γ production from activated B cells. Proc Natl Acad Sci USA 94:3948–3953, 1997Google Scholar
  115. 115.
    Lauwerys BR, Renauld JC, Houssiau FA: Inhibition of in vitro immunoglobulin production by IL-12 in murine chronic graft-vs.-host disease: Synergism with IL-18. Eur J Immunol 28:2017–2024, 1998Google Scholar
  116. 116.
    Ohtsuki T, Micallef MJ, Kohno K, Tanimoto T, Ikeda M, Kurimoto M: Interleukin-18 enhances Fas ligand expression and induces apoptosis in Fas-expressing human myelomonocytic KG-1 cells. Anticancer Res 17:3253–3258, 1997Google Scholar
  117. 117.
    Dao T, Ohashi K, Kayano T, Kurimoto M, Okamura H: Interferon-γ-inducing factor, a novel cytokine, enhances Fas ligand-mediated cytotoxicity of murine T helper cells. Cell Immunol 173:230–235, 1997Google Scholar
  118. 118.
    Dao T, Mehal WZ, Crispe IN: IL-18 augments perforin-dependent cytotoxicity of liver NK-T cells. J Immunol 161:2217–2222, 1998Google Scholar
  119. 119.
    Kohka H, Yoshino T, Iwagaki H, Sakuma I, Tanimoto T, Matsuo Y, Kurimoto M, Orita K, Akagi T, Tanaka N: Interleukin-18/interferon-γ-inducing factor, a novel cytokine, up-regulates ICAM-1 (CD54) expression in KG-1 cells. J Leukoc Biol 64:519–527, 1998Google Scholar

Copyright information

© Plenum Publishing Corporation 1999

Authors and Affiliations

  • Giamila Fantuzzi
    • 1
  • Charles A. Dinarello
    • 1
  1. 1.Department of Medicine, Division of Infectious DiseasesUniversity of Colorado Health Sciences CenterDenver

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