Interleukin-18: Recent advances

Current Opinion in Hematology

Volumn 11, Issue 6, 2004, Pages 405-410

  Reddy, Pavan ^a  

^a UNIVERSITY OF MICHIGAN COMPREHENSIVE CANCER CENTER   (United States)

Author keywords

Dendritic cells; GVHD; IDDM; IL 18; Sepsis; T cells

Indexed keywords

GAMMA INTERFERON; INTERLEUKIN 1; INTERLEUKIN 18; INTERLEUKIN 18 RECEPTOR; STAT4 PROTEIN; TUMOR NECROSIS FACTOR ALPHA;

ACUTE GRAFT REJECTION; AUTOIMMUNE DISEASE; CELL FUNCTION; CELL MATURATION; CELL POLARITY; COMPLEX FORMATION; CYTOKINE PRODUCTION; DENDRITIC CELL; EXON; GENE CONTROL; GENE STRUCTURE; GENOTYPE; GRAFT VERSUS HOST REACTION; HUMAN; IMMUNE RESPONSE; IMMUNOBIOLOGY; IMMUNOMODULATION; INFLAMMATORY DISEASE; INSULIN DEPENDENT DIABETES MELLITUS; NATURAL KILLER CELL; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN STRUCTURE; PROTEIN TERTIARY STRUCTURE; RECEPTOR BINDING; REVIEW; SEPSIS; TH1 CELL; UPREGULATION;

ANIMALS; DIABETES MELLITUS, TYPE 1; HUMANS; INFLAMMATION; INTERLEUKIN-18; SEPSIS; SIGNAL TRANSDUCTION; TH1 CELLS; TH2 CELLS;

EID: 8544275811     PISSN: 10656251     EISSN: None     Source Type: Journal    
DOI: 10.1097/01.moh.0000141926.95319.42     Document Type: Review

References (81)

1. Okamura H, Tsutsi H, Komatsu T, et al.: Cloning of a new cytokine that induces IFN-gamma production by T cells. Nature 1995, 378:88-91.
2. Nakanishi K, Yoshimoto T, Tsutsui H, et al.: Interleukin-18 regulates both Th1 and Th2 responses. Annu Rev Immunol 2001, 19:423-474.
3. Torigoe K, Ushio S, Okura T, et al.: Purification and characterization of the human interleukin-18 receptor. Am Soc Biochem Mol Biol 1997, 272:25737-25742.
4. Hoshino K, Tsutsui H, Kawai T, et al.: Cutting edge: generation of IL-18 receptor-deficient mice: evidence for IL-1 receptor-related protein as an essential IL-18 binding receptor. J Immunol 1999, 162:5041-5044.
5. Gerdes N, Sukhova GK, Libby P, et al.: Expression of interleukin (IL)-18 and functional IL-18 receptor on human vascular endothelial cells, smooth muscle cells, and macrophages: implications for atherogenesis. J Exp Med 2002, 195:245-257.
6. Leung BP, Culshaw S, Gracie JA, et al.: A role for IL-18 in neutrophil activation. J Immunol 2001, 167:2879-2886.
7. Leung W, Iyengar R, Turner V, et al.: Determinants of antileukemia effects of allogeneic NK cells. J Immunol 2004, 172:644-650.
8. Azam T, Novick D, Bufler P, et al.: Identification of a critical Ig-like domain in IL-18 receptor alpha and characterization of a functional IL-18 receptor complex. J Immunol 2003, 171:6574-6580.
9. Sims JE: IL-1 and IL-18 receptors, and their extended family. Curr Opin Immunol 2002, 14:117-122.
10. Akira S: Mammalian toll-like receptors. Curr Opin Immunol 2003, 15:5-11.
11. Adachi O, Kawai T, Takeda K, et al.: Targeted disruption of the MyD88 gene results in loss of IL-1 and IL-18 mediated function. Immunity 1998, 9:143-150.
12. Kojima H, Takeuchi M, Ohta T, et al.: Interleukin-18 activates the IRAK-TRAF6 pathway in mouse EL-4 cells. Biochem Biophys Res Commun 1998, 244:183-186.
13. Kanakaraj P, Ngo K, Wu Y, et al.: Defective interleukin (IL)-18-mediated natural killer and T helper cell type 1 responses in IL-1 receptor-associated kinase (IRAK)-deficient mice. J Exp Med 1999, 189:1129-1138.
14. Suzuki N, Chen NJ, Millar DG, et al.: IL-1 receptor-associated kinase 4 is essential for IL-18-mediated NK and Th1 cell responses. J Immunol 2003, 170:4031-4035. This study showed that Th1 cells from IL-1R-associated kinase-4-deficient mice did not exhibit NF-κB activation or IκB degradation or activator protein-1 activation in response to IL-18 and IL-18-induced NK, Th1 responses were impaired.
15. Kojima H, Aizawa Y, Yanai Y, et al.: An essential role for NF-kappa B in IL-18-induced IFN-gamma expression in KG-1 cells. J Immunol 1999, 162:5063-5069.
16. Matsumoto S, Tsuji-Takayama K, Aizawa Y, et al.: Interleukin-18 activates NF-kappaB in murine T helper type 1 cells. Biochem Biophys Res Commun 1997, 234:454-457.
17. Yu JJ, Tripp CS, Russell JH: Regulation and phenotype of an innate Th1 cell: role of cytokines and the p38 kinase pathway. J Immunol 2003, 171:6112-6118.
18. Yang J, Zhu H, Murphy TL, et al.: IL-18-stimulated GADD45 beta required in cytokine-induced, but not TCR-induced, IFN-gamma production. Nat Immunol 2001, 2:157-164.
19. Shimoda K, Tsutsui H, Aoki K, et al.: Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice. Blood 2002, 99:2094-2099.
20. Sugimoto N, Nakahira M, Ahn HJ, et al.: Differential requirements for JAK2 and TYK2 in T cell proliferation and IFN-gamma production induced by IL-12 alone or together with IL-18. Eur J Immunol 2003, 33:243-251.
21. Nakahira M, Tomura M, Iwasaki M, et al.: An absolute requirement for STAT4 and a role for IFN-gamma as an amplifying factor in IL-12 induction of the functional IL-18 receptor complex. J Immunol 2001, 167:1306-1312.
22. Nakahira M, Ahn HJ, Park WR, et al.: Synergy of IL-12 and IL-18 for IFN-gamma gene expression: IL-12-induced STAT4 contributes to IFN-gamma promoter activation by up-regulating the binding activity of IL-18-induced activator protein 1. J Immunol 2002, 168:1146-1153.
23. Lee JK, Kim SH, Lewis EC, et al.: Differences in signaling pathways by IL-1β and IL-18. Proc Natl Acad Sci U S A 2004, 101:8815-8820. This paper demonstrates that signaling pathways between IL-18 and IL-1 are distinct as an explanation for the ability of IL-1 to cause fever.
24. Kato Z, Jee J, Shikano H, et al.: The structure and binding mode of interleukin-18. Nat Struct Biol 2003, 10:966-971. This study determined the solution structure of IL-18 by nuclear magnetic resonance spectroscopy and mutagenesis studies, and showed that the mode of interaction between IL-18 and IL-18Rα is similar to that seen in the IL-1β/IL-1Rα binary complex. It also demonstrated residues in the structure of IL-18 that are important for binding IL-18Rβ to the binary complex.
25. Yamamoto Y, Kato Z, Matsukuma E, et al.: Generation of highly stable IL-18 based on a ligand-receptor complex structure. Biochem Biophys Res Commun 2004, 317:181-186.
26. Tone M, Thompson SA, Tone Y, et al.: Regulation of IL-18 (IFN-gamma-inducing factor) gene expression. J Immunol 1997, 159:6156-6163.
27. Puren AJ, Fantuzzi G, Dinarello CA: Gene expression, synthesis, and secretion of interleukin 18 and interleukin 1beta are differentially regulated in human blood mononuclear cells and mouse spleen cells. Proc Natl Acad Sci USA 1999, 96:2256-2261.
28. Kalina U, Ballas K, Koyama N, et al.: Genomic organization and regulation of the human interleukin-18 gene. Scand J Immunol 2000, 52:525-530.
29. Koyama N, Hoelzer D, Ottmann OG: Regulation of human IL-18 gene expression: interaction of PU.1 with GC-box binding protein is involved in human IL-18 expression in myeloid cells. Eur J Immunol 2004, 34:817-826.
30. Kim YM, Im JY, Han SH, et al.: IFN-gamma up-regulates IL-18 gene expression via IFN consensus sequence-binding protein and activator protein-1 elements in macrophages. J Immunol 2000, 165:3198-3205.
31. Kim YM, Kang HS, Paik SG, et al.: Roles of IFN consensus sequence binding protein and PU.1 in regulating IL-18 gene expression. J Immunol 1999, 163:2000-2007.
32. Wald D, Qin J, Zhao Z, et al.: SIGIRR, a negative regulator of toll-like receptor-interleukin 1 receptor signaling. Nat Immunol 2003, 4:920-927. The authors show that an orphan from the IL-1 superfamily of receptors, SIGIRR, inhibits cellular activation by IL-1, LPS, and IL-18. SIGIRR could therefore be a negative regulator of the detrimental effects of immune activation.
33. Takeda N, Arima M, Tsuruoka N, et al.: Bcl6 is a transcriptional repressor for the IL-18 gene. J Immunol 2003, 171:426-431.
34. Hurgin V, Novick D, Rubinstein M: The promoter of IL-18 binding protein: activation by an IFN-gamma-induced complex of IFN regulatory factor 1 and CCAAT/enhancer binding protein beta. Proc Natl Acad Sci USA 2002, 99:16957-16962.
35. Gu Y, Kuida K, Tsutsui H, et al.: Activation of interferon-γ inducing factor mediated by interleukin-1β converting enzyme. Science 1997, 275:206-209.
36. Sugawara S, Uehara A, Nochi T, et al.: Neutrophil proteinase 3-mediated induction of bioactive IL-18 secretion by human oral epithelial cells. J Immunol 2001, 167:6568-6575.
37. Akita K, Ohtsuki T, Nukada Y, et al.: 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 1997, 272:26595-26603.
38. Hentze H, Lin XY, Choi MS, et al.: Critical role for cathepsin B in mediating caspase-1-dependent interleukin-18 maturation and caspase-1- independent necrosis triggered by the microbial toxin nigericin. Cell Death Differ 2003, 10:956-968.
39. Yoshimoto T, Mizutani H, Tsutsui H, et al.: IL-18 induction of IgE: dependence on CD4+ T cells, IL-4 and STAT6. Nat Immunol 2000, 1:132-137.
40. Yoshimoto T, Min B, Sugimoto T, et al.: Nonredundant roles for CD1d-restricted natural killer T cells and conventional CD4+ T cells in the induction of immunoglobulin E antibodies in response to interleukin 18 treatment of mice. J Exp Med 2003, 197:997-1005. The authors demonstrate that NK T cells are the primary sources of IL-4 and that they are critical for IL-18-induced Th2 polarization.
41. Xu D, Trajkovic V, Hunter D, et al.: IL-18 induces the differentiation of Th1 or Th2 cells depending upon cytokine milieu and genetic background. Eur J Immunol 2000, 30:3147-3156.
42. Sugimoto T, Ishikawa Y, Yoshimoto T, et al.: Interleukin 18 acts on memory T helper cells type 1 to induce airway inflammation and hyperresponsiveness in a naive host mouse. J Exp Med 2004, 199:535-545. This study demonstrates a role for Th1 cells and IL-18 in mediating an allergic disease.
43. Berg RE, Crossley E, Murray S, et al.: Memory CD8+ T cells provide innate immune protection against Listeria monocytogenes in the absence of cognate antigen. J Exp Med 2003, 198:1583-1593. This paper shows that the IL-12 and IL-18 receptors are upregulated on memory CD8+ T cells, and that these cells can mediate an antigen-nonspecific innate immune response.
44. Liew FY, Wei XQ, McInnes IB: Role of interleukin 18 in rheumatoid arthritis. Ann Rheum Dis 2003, 62(suppl 2):ii48-ii50. This review provides a good summary of the role of IL-18 in rheumatoid arthritis.
45. Ishida Y, Kondo T, Takayasu T, et al.: The essential involvement of cross-talk between IFN-gamma and TGF-beta in the skin wound-healing process. J Immunol 2004, 172:1848-1855.
46. Schneider E, Tonanny MB, Lisbonne M, et al.: Pro-Th1 cytokines promote Fas-dependent apoptosis of immature peripheral basophils. J Immunol 2004, 172:5262-5268.
47. Chandrasekar B, Vemula K, Surabhi RM, et al.: Activation of intrinsic and extrinsic proapoptotic signaling pathways in interleukin-18-mediated human cardiac endothelial cell death. J Biol Chem 2004, 279:20221-20233.
48. Finotto S, Siebler J, Hausding M, et al.: Severe hepatic injury in interleukin 18 (IL-18) transgenic mice: a key role for IL-18 in regulating hepatocyte apoptosis in vivo. Gut 2004, 53:392-400.
49. Andrews DM, Scalzo AA, Yokoyama WM, et al.: Functional interactions between dendritic cells and NK cells during viral infection. Nat Immunol 2003, 4:175-181. This paper demonstrates an interaction between NK cells and DCs. The authors demonstrate that IL-18 and IL-12 play a critical role in mediating the cross-talk between these cellular subsets.
50. Kaser A, Kaser S, Kaneider NC, et al.: Interleukin-18 attracts plasmacytoid dendritic cells (DC2s) and promotes Th1 induction by DC2s through IL-18 receptor expression. Blood 2004, 103:648-655.
51. Fantuzzi G, Banda NK, Guthridge C, et al.: Generation and characterization of mice transgenic for human IL-18-binding protein isoform a. J Leukoc Biol 2003, 74:889-896. This paper describes the generation and phenotype of human IL-18BP transgenic mice.
52. Gracie JA, Robertson SE, McInnes IB: Interleukin-18. J Leukoc Biol 2003, 73:213-224.
53. Kanai T, Uraushihara K, Totsuka T, et al.: Macrophage-derived IL-18 targeting for the treatment of Crohn's disease. Curr Drug Targets Inflamm Allergy 2003, 2:131-136.
54. Dinarello CA, Novick D, Rubinstein M, et al.: Interleukin 18 and interleukin 18 binding protein: possible role in immunosuppression of chronic renal failure. Blood Purif 2003, 21:258-270.
55. Dinarello CA, Fantuzzi G: Interleukin-18 and host defense against infection. J Infect Dis 2003, 187(suppl 2):S370-S384. This paper provides a comprehensive review on the role of IL-18 in infectious diseases.
56. Hu HZ, Li GL, Lim YK, et al.: Kinetics of interferon-gamma secretion and its regulatory factors in the early phase of acute graft-versus-host disease. Immunology 1999, 98:379-385.
57. Itoi H, Fujimori Y, Tsutsui H, et al.: Fas ligand-induced caspase-1-dependent accumulation of interleukin-18 in mice with acute graft-versus-host disease. Blood 2001, 98:235-237.
58. Fujimori Y, Takatsuka H, Takemoto Y, et al.: Elevated interleukin (IL)-18 levels during acute graft-versus-host disease after allogeneic bone marrow transplantation. Br J Haematol 2000, 109:652-657.
59. Zecchina G, Novick D, Rubinstein M, et al.: Interleukin-18 binding protein in acute graft versus host disease and engraftment following allogeneic peripheral blood stem cell transplants. J Hematother Stem Cell Res 2001, 10:769-776.
60. Reddy P, Teshima T, Kukuruga M, et al.: Interleukin-18 regulates acute graft-versus-host disease by enhancing Fas-mediated donor T cell apoptosis. J Exp Med 2001, 194:1433-1440.
61. Reddy P, Ferrara JL: Role of interleukin-18 in acute graft-vs-host disease. J Lab Clin Med 2003, 141:365-371. This review summarizes the role of IL-18 on acute GVHD.
62. Okamoto I, Kohno K, Tanimoto T, et al.: IL-18 prevents the development of chronic graft-versus-host disease in mice. J Immunol 2000, 164:6067-6074.
63. Reddy P, Teshima T, Hildebrandt G, et al.: Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects. Blood 2003, 101:2877-2885.
64. Itoi H, Fujimori Y, Tsutsui H, et al.: Differential upregulation of interleukin-18 receptor alpha chain between CD4+ and CD8+ T cells during acute graft-versus-host disease in mice. J Interferon Cytokine Res 2004, 24:291-296.
65. Fujimori Y, Yoshimoto T, Matsui K, et al.: Increased expression of interleukin-18 receptor on T lymphocytes in patients with acute graft-versus-host disease after allogeneic bone marrow transplantation. J Interferon Cytokine Res 2002, 22:751-754.
66. Arnold D, Wasem C, Juillard P, et al.: IL-18-independent cytotoxic T lymphocyte activation and IFN-gamma production during experimental acute graft-versus-host disease. Int Immunol 2002, 14:503-511.
67. Rothe H, Jenkins NA, Copeland NG, et al.: Active stage of autoimmune diabetes is associated with the expression of a novel cytokine, IGIF, which is located near Idd2. J Clin Invest 1997, 99:469-474.
68. Rothe H, Hausmann A, Casteels K, et al.: IL-18 inhibits diabetes development in nonobese diabetic mice by counterregulation of Th1-dependent destructive insulitis. J Immunol 1999, 163:1230-1236.
69. Oikawa Y, Shimada A, Kasuga A, et al.: Systemic administration of IL-18 promotes diabetes development in young nonobese diabetic mice. J Immunol 2003, 171:5865-5875.
70. Nicoletti F, Di Marco R, Papaccio G, et al.: Essential pathogenic role of endogenous IL-18 in murine diabetes induced by multiple low doses of streptozotocin. Prevention of hyperglycemia and insulitis by a recombinant IL-18-binding protein: Fc construct. Eur J Immunol 2003, 33:2278-2286.
71. Schott WH, Haskell BD, Tse HM, et al.: Caspase-1 is not required for type 1 diabetes in the NOD mouse. Diabetes 2004, 53:99-104.
72. Nicoletti F, Conget I, Di Marco R, et al.: Serum levels of the interferon-gamma-inducing cytokine interleukin-18 are increased in individuals at high risk of developing type I diabetes. Diabetologia 2001, 44:309-311.
73. Ide A, Kawasaki E, Abiru N, et al.: Association of interleukin-18 gene promoter polymorphisms in type 1 diabetes and autoimmune thyroid disease. Ann N Y Acad Sci 2003, 1005:436-439.
74. Kretowski A, Mironczuk K, Karpinska A, et al.: Interleukin-18 promoter polymorphisms in type 1 diabetes. Diabetes 2002, 51:3347-3349.
75. Ide A, Kawasaki E, Abiru N, et al.: Association between IL-18 gene promoter polymorphisms and CTLA-4 gene 49A/G polymorphism in Japanese patients with type 1 diabetes. J Autoimmun 2004, 22:73-78.
76. Nolsoe RL, Pociot F, Novick D, et al.: Mutation scan of a type 1 diabetes candidate gene: the human interleukin-18 binding protein gene. Ann N Y Acad Sci 2003, 1005:332-339.
77. Endo S, Inada K, Yamada Y, et al.: Interleukin 18 (IL-18) levels in patients with sepsis. J Med 2000, 31:15-20.
78. Feezor RJ, Oberholzer C, Baker HV, et al.: Molecular characterization of the acute inflammatory response to infections with Gram-negative versus Gram-positive bacteria. Infect Immunol 2003, 71:5803-5813.
79. Oberholzer A, Steckholzer U, Kurimoto M, et al.: Interleukin-18 plasma levels are increased in patients with sepsis compared to severely injured patients. Shock 2001, 16:411-414.
80. Remick DG, Bolgos GE, Siddiqui J: Inflammatory status in sepsis alters efficacy of interleukin-18 binding protein therapy. Crit Care Med 2003, 31:2096-2101.
81. Stassen NA, Breit CM, Norfleet LA, et al.: IL-18 promoter polymorphisms correlate with the development of post-injury sepsis. Surgery 2003, 134:351-356.