Interleukin 6 in autoimmune and inflammatory diseases: A personal memoir

Proceedings of the Japan Academy Series B: Physical and Biological Sciences

Volumn 86, Issue 7, 2010, Pages 717-730

  Hirano, Toshio ^a,b  

^a JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

^b Institute of Physical and Chemical Research   (Japan)

Author keywords

Autoimmune disease; Cytokine; Immune response; Inflammation; Interleukin 6; Rheumatoid arthritis

Indexed keywords

INTERLEUKIN 6;

ANIMAL; AUTOIMMUNE DISEASE; HISTORY; HUMAN; HUMAN T CELL LEUKEMIA VIRUS 1; IMMUNOLOGY; INFLAMMATION; METABOLISM; PATHOPHYSIOLOGY; REVIEW; RHEUMATOID ARTHRITIS;

ANIMALS; ARTHRITIS, RHEUMATOID; AUTOIMMUNE DISEASES; HISTORY, 20TH CENTURY; HUMAN T-LYMPHOTROPIC VIRUS 1; HUMANS; INFLAMMATION; INTERLEUKIN-6;

HUMAN T-LYMPHOTROPIC VIRUS 1; MUS;

EID: 77957861314     PISSN: 03862208     EISSN: 13492896     Source Type: Journal    
DOI: 10.2183/pjab.86.717     Document Type: Review

References (76)

1. Marrack, P., Kappler, J. and Kotzin, B. (2001) Autoimmune disease: why and where it occurs. Nat. Med. 7, 899-905.
2. Ermann, J. and Fathman, C.G. (2001) Autoimmune diseases: genes, bugs and failed regulation. Nat. Immunol. 2, 759-761.
3. O'Shea, J.J., Ma, A. and Lipsky, P. (2002) Cytokines and autoimmunity. Nat. Rev. Immunol. 2, 37-45.
4. Mathis, D. and Benoist, C. (2004) Back to central tolerance. Immunity 20, 509-516.
5. Mocci, S., Lafferty, K. and Howard, M. (2000) The role of autoantigens in autoimmune disease. Curr. Opin. Immunol. 12, 725-730.
6. Skapenko, A., Leipe, J., Lipsky, P.E. and Schulze-Koops, H. (2005) The role of the T cell in autoimmune inflammation. Arthritis Res. Ther. 7, S4-S14.
7. Hirano, T. (1998) Interleukin 6 and its receptor: ten years later. Int. Rev. Immunol. 16, 249-284.
8. Matsumoto, I., Staub, A., Benoist, C. and Mathis, D. (1999) Arthritis Provoked by Linked T and B Cell Recognition of a Glycolytic Enzyme. Science 286, 1732-1735.
9. Hirano, T. (2002) Cytokines in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev. 13, 297-298.
10. Hirano, T. (2002) Revival of the autoantibody model in rheumatoid arthritis. Nat. Immunol. 3, 342-344.
11. Hirano, T., Matsuda, T., Turne, M., Miyasaka, N., Buchan, G., Tang, B. et al. (1988) Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur. J. Immunol. 18, 1797-1801.
12. Ishihara, K. and Hirano, T. (2002) IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev. 13, 357-368.
13. Andreakos, E., Foxwell, B., Brennan, F., Maini, R. and Feldmann, M. (2002) Cytokines and anticytokine biologicals in autoimmunity: present and future. Cytokine Growth Factor Rev. 13, 299-313.
14. Feldmann, M., Brennan, F. and Maini, R. (1996) Role of cytokines in rheumatoid arthritis. Annu. Rev. Immunol. 14, 397-440.
15. Feldmann, M. and Maini, R.N. (2001) Anti-TNF alpha therapy of rheumatoid arthritis: what have we learned? Annu. Rev. Immunol. 19, 163-196.
16. Nishimoto, N., Kishimoto, T. and Yoshizaki, K. (2000) Anti-interleukin 6 receptor antibody treatment in rheumatic disease. Ann. Rheum. Dis. 59, i21-i27.
17. Nishimoto, N. and Kishimoto, T. (2004) Inhibition of IL-6 for the treatment of inflammatory diseases. Curr. Opin. Pharmacol. 4, 386-391.
18. Atsumi, T., Ishihara, K., Kamimura, D., Ikushima, H., Ohtani, T., Hirota, S. et al. (2002) A point mutation of Tyr-759 in interleukin 6 family cytokine receptor subunit gp130 causes autoimmune arthritis. J. Exp. Med. 196, 979-990.
19. Sawa, S., Kamimura, D., Jin, G.H., Morikawa, H., Kamon, H., Nishihara, M. et al. (2006) Autoimmune arthritis associated with mutated interleukin (IL)-6 receptor gp130 is driven by STAT3/IL-7-dependent homeostatic proliferation of CD4+ T cells. J. Exp. Med. 12, 1459-1470.
20. Hata, H., Sakaguchi, N., Yoshitomi, H., Iwakura, Y., Sekikawa, K., Azuma, Y. et al. (2004) Distinct contribution of IL-6, TNF-alpha, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice. J. Clin. Invest. 114, 582-588.
21. Alonzi, T., Fattori, E., Lazzaro, D., Costa, P., Probert, L., Kollias, G. et al. (1998) Interleukin 6 is required for the development of collagen-induced arthritis. J. Exp. Med. 187, 461-468.
22. Ohshima, S., Saeki, Y., Mima, T., Sasai, M., Nishioka, K., Nomura, S. et al. (1998) Interleukin 6 plays a key role in the development of antigeninduced arthritis. Proc. Natl. Acad. Sci. USA 95, 8222-8226.
23. Murakami, M., Kamimura, D. and Hirano, T. (2004) New IL-6 (gp130) family cytokine members, CLC/NNT1/BSF3 and IL-27. Growth Factors 2004, 2.
24. Kamimura, D., Ishihara, K. and Hirano, T. (2003) IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev. Physiol. Biochem. Pharmacol. 149, 1-38.
25. Fukada, T., Hibi, M., Yamanaka, Y., Takahashi-Tezuka, M., Fujitani, Y., Yamaguchi, T. et al. (1996) Two signals are necessary for cell proliferation induced by a cytokine receptor gp130: involvement of STAT3 in anti-apoptosis. Immunity 5, 449-460.
26. Ohtani, T., Ishihara, K., Atsumi, T., Nishida, K., Kaneko, Y., Miyata, T. et al. (2000) Dissection of signaling cascades through gp130 in vivo: Reciprocal roles for STAT3-and SHP2-mediated signals in immune responses. Immunity 12, 95-105.
27. Cua, D.J., Sherlock, J., Chen, Y., Murphy, C.A., Joyce, B., Seymour, B. et al. (2003) Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 421, 744-748.
28. + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages. Nat. Immunol. 6, 1123-1132.
29. Park, H., Li, Z., Yang, X.O., Chang, S.H., Nurieva, R., Wang, Y.H. et al. (2005) A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17. Nat. Immunol. 6, 1133-1141.
30. Veldhoen, M., Hocking, R., Atkins, C., Locksley, R. and Stockinger, B. (2006) TGF in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity 24, 179-189.
31. Bettelli, E., Carrier, Y., Gao, W., Korn, T., Strom, T., Oukka, M. et al. (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235-238.
32. Mangan, P.R., Harrington, L.E., O'Quinn, D.B., Helms, W.S., Bullard, D.C., Elson, C.O. et al. (2006) Transforming growth factor-beta induces development of the T(H)17 lineage. Nature 441, 231-234.
33. Ivanov, I.I., McKenzie, B.S., Zhou, L., Tadokoro, C.E., Lepelley, A., Lafaille, J.J. et al. (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121-1133.
34. Nishihara, M., Ogura, H., Ueda, N., Tsuruoka, M., Kitabayashi, C., Tsuji, F. et al. (2007) IL-6-gp130-STAT3 in T cells directs the development of IL-17+ Th with a minimum effect on that of Treg in the steady state. Int. Immunol. 19, 695-702.
35. Linterman, M.A. and Vinuesa, C.G. (2010) Signals that influence T follicular helper cell differentiation and function. Semin. Immunopathol. (in press).
36. Dutton, R.W., Falkoff, R., Hirst, J.A., Hoffman, M., Kappler, J.W., Kattman, J.F. et al. (1971) Is there evidence for a nonantigen specific diffusable chemical mediator from the thymus-derived cell in the initiation of the immune response? Pro. Immunol. 1, 355.
37. Schimpl, A. and Wecker, E. (1972) Replacement of T cell function by a T cell product. Nat. New Biol. 235, 15-17.
38. Hirano, T., Teranishi, T., Toba, T., Sakaguchi, N., Fukukawa, T. and Tsuyuguchi, I. (1981) Human helper T cell factor(s) (ThF). I. Partial purification and characterization. J. Immunol. 126, 517-522.
39. Muraguchi, A., Kishimoto, T., Miki, Y., Kuritani, T., Kaieda, T., Yoshizaki, K. et al. (1981) T cell-replacing factor(TRF)-induced IgG secretion in human B blastoid cell line and demonstration of acceptors for TRF. J. Immunol. 127, 412-416.
40. Teranishi, T., Hirano, T., Arima, N. and Onoue, K. (1982) Human helper T cell factor(s) (ThF). II. Induction of IgG production in B lymphoblastoid cell lines and identification of T cell replacing factor (TRF)-like factor(s). J. Immunol. 128, 1903-1908.
41. Okada, M., Sakaguchi, N., Yoshimura, N., Hara, H., Shimizu, K., Yoshida, N. et al. (1983) B cell growth factor and B cell differentiation factor from human T hybridomas: Two distinct kinds of BCGFs and their synergism in B cell proliferation. J. Exp. Med. 157, 583-590.
42. Hirano, T., Teranishi, T. and Onoue, K. (1984) Human helper T cell factor(s). III. Characterization of B cell differentiation factor I (BCDF I). J. Immunol. 132, 229-234.
43. Hirano, T., Teranishi, T., Lin, B. and Onoue, K. (1984) Human helper T cell factor(s). IV. Demonstration of a human late-acting B cell differentiation factor acting on Staphylococcus aureus Cowan I-stimulated B cells. J. Immunol. 133, 798-802.
44. Hirano, T., Taga, T., Nakano, N., Yasukawa, K., Kashiwamura, S., Shimizu, K. et al. (1985) Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc. Natl. Acad. Sci. USA 82, 5490-5494.
45. Hirano, T., Taga, T., Yasukawa, K., Nakajima, K., Nakano, N., Takatsuki, F. et al. (1987) Human B cell differentiation factor defined by an antipeptide antibody and its possible role in autoantibody production. Proc. Natl. Acad. Sci. USA 84, 228-231.
46. Hirano, T., Yasukawa, K., Harada, H., Taga, T., Watanabe, Y., Matsuda, T. et al. (1986) Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324, 73-76.
47. Haegeman, G., Content, J., Volckaert, G., Derynck, R., Tavernier, J. and Fiers, W. (1986) Structural analysis of the sequence encoding for an inducible 26-kDa protein in human fibroblasts. Eur. J. Biochem. 159, 625-632.
48. Zilberstein, A., Ruggieri, R., Korn, J.H. and Revel, M. (1986) Structure and expression of cDNA and genes for human interferon-β-2, a distinct species inducible by growth-stimulatory cytokines. EMBO J. 5, 2529-2537.
49. Marx, J.L. (1988) Orphan interferon finds a new home. Science 239, 25-26.
50. Sehgal, P.B., May, T.T., Tamm, I. and Vilcek, J. (1987) Human β2 interferon and B-cell differentiation factor BSF-2 are identical. Science 235, 731-732.
51. Andus, T., Geiger, T., Hirano, T., Northoff, H., Ganter, U., Bauer, J. et al. (1987) Recombinant human B cell stimulatory factor 2 (BSF-2/IFN-beta 2) regulates β-fibrinogen and albumin mRNA levels in Fao-9 cells. FEBS Lett. 221, 18-22.
52. Gauldie, J., Richards, C., Harnish, D., Lansdorp, P. and Baumann, H. (1987) Interferon β2/B-cell stimulatory factor type 2 shares identity with monocyte-derived hepatocyte-stimulating factor and regulates the major acute phase protein response in liver cells. Proc. Natl. Acad. Sci. USA 84, 7251-7255.
53. Van Damme, J., Opdenakker, G., Simpson, R.J., Rubira, M.R., Cayphas, S., Vink, A. et al. (1987) Dentification of the human 26-kDa protein, interferon β2 (IFN β2), as a B cell hybridoma/plasmacytoma growth factor induced by interleukin 1 and tumor necrosis factor. J. Exp. Med. 165, 914-919.
54. Kawano, M., Hirano, T., Matsuda, T., Taga, T., Horii, Y., Iwato, K. et al. (1988) Autocrine generation and requirement of BSF-2/IL-6 for human multiple myelomas. Nature 332, 83-85.
55. Van Snick, J., Cayphas, S., Szikora, J.P., Renauld, J.C., Van Roost, E., Boon, T. et al. (1988) cDNA cloning of murine interleukin-HP1:homology with human interleukin 6. Eur. J. Immunol. 18, 193-197.
56. Sehgal, P.B., Grienger, G. and Tosato, G. (eds.) (1989) Regulation of the acute phase and immune responses: Interleukin-6. Ann. New York Acad. Sci. 557, 1-583.
57. Noma, Y., Sideras, P., Naito, T., Bergstedt-Lindquist, S., Azuma, C., Severinson, E. et al. (1986) Cloning of cDNA encoding the murine IgG1 induction factor by a novel strategy using SP6 promoter. Nature 319, 640-646.
58. Kinashi, T., Harada, N., Severinson, E., Tanabe, T., Sideras, P., Konishi, M. et al. (1986) Cloning of complementary DNA encoding T-cell replacing factor and identity with B-cell growth factor II. Nature 324, 70-73.
59. Hirano, T. and Kishimoto, T. (1990) Interleukin-6. Handbook of Experimental Pharmacology 95/I, 633-665.
60. Van Snick, J. (1990) Interleukin-6: an overview. Annu. Rev. Immunol. 8, 253-278.
61. Heinrich, P.C., Castell, J.V. and Andus, T. (1990) Interleukin-6 and the acute phase response. Biochem. J. 265, 621-636.
62. Yamasaki, K., Taga, T., Hirata, Y., Yawata, H., Kawanishi, Y., Seed, B. et al. (1988) Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science 241, 825-828.
63. Hibi, M., Murakami, M., Saito, M., Hirano, T., Taga, T. and Kishimoto, T. (1990) Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 63, 1149-1157.
64. Taga, T., Hibi, M., Hirata, Y., Yamasaki, K., Yasukawa, K., Matsuda, T. et al. (1989) Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 58, 573-581.
65. Hirano, T. (1992) Interleukin-6 and its relation to inflammation and disease. Clin. Immunol. Immunopathol. 62, S60-S65.
66. Iwakura, Y., Tosu, M., Yoshida, E., Takiguchi, M., Sato, K., Kitajima, I. et al. (1991) Induction of inflammatory arthropathy resembling rheumatoid arthritis in mice transgenic for HTLV-I. Science 253, 1026-1028.
67. Ishihara, K., Sawa, S., Ikushima, H., Hirota, S., Atsumi, T., Kamimura, D. et al. (2004) The point mutation of tyrosine 759 of the IL-6 family cytokine receptor gp130 synergizes with HTLV-1 pX in promoting rheumatoid arthritis-like arthritis. Int. Immunol. 16, 455-465.
68. Zhu, J., Yamane, H., Cote-Sierra, J., Guo, L. and Paul, W.E. (2006) GATA-3 promotes Th2 responses through three different mechanisms: induction of Th2 cytokine production, selective growth of Th2 cells and inhibition of Th1 cell-specific factors. Cell Res. 16, 3-10.
69. Mosmann, T.R. and Coffman, R.L. (1989) TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. Immunol. 7, 145-173.
70. Glimcher, L.H. and Murphy, K.M. (2000) Lineage commitment in the immune system: the T helper lymphocyte grows up. Genes Dev. 14, 1693-1711.
71. Iwakura, Y. and Ishigame, H. (2006) The IL-23/IL-17 axis in inflammation. J. Clin. Invest. 116, 1218-1222.
72. + Th cells that cause autoimmune arthritis. J. Exp. Med. 204, 41-47.
73. H-17 cells in the circle of immunity and autoimmunity. Nat. Immunol. 8, 345-350.
74. Afzali, B., Lombardi, G., Lechler, R.I. and Lord, G.M. (2007) The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease. Clin. Exp. Immunol. 148, 32-46.
75. Ogura, H., Murakami, M., Okuyama, Y., Tsuruoka, M., Kitabayashi, C., Kanamoto, M. et al. (2008) Interleukin-17 Promotes Autoimmunity by Triggering a Positive-Feedback Loop via Interleukin-6 Induction. Immunity 29, 628-636.
76. Sakaguchi, S. (2000) Regulatory T cells: key controllers of immunologic self-tolerance. Cell 101, 455-458.