Skip to main content
SpringerLink
Log in

Clinical studies in patients with Castleman’s disease, Crohn’s disease, and rheumatoid arthritis in Japan

  • Published:
Clinical Reviews in Allergy & Immunology Aims and scope Submit manuscript

Abstract

Interleukin (IL)-6 is a pleiotropic cytokine with a wide range of biological activities and regulates immunological reactions, inflammatory responses, and hematopoiesis. Overproduction of IL-6 has been shown to be pathologically involved in some inflammatory diseases, such as Castleman’s disease, Crohn’s disease, and rheumatoid arthritis. Clinical studies have been conducted to investigate a role of IL-6 and the therapeutic potential of anti-IL-6 therapy for these diseases using humanized anti-IL-6 receptor antibody (tocilizumab; currently known as MRA). Overall, tocilizumab was well-tolerated, and improvements of signs and symptoms were observed, confirming the pathological role of IL-6 and suggesting that the blockade of IL-6 could become a new and important treatment option in these refractory diseases.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Dickman, S. (1998), Science 280, 1196, 1197.

    Article  PubMed  CAS  Google Scholar 

  2. Akira, S., Taga, T., and Kishimoto, T. (1993), Adv. Immunol. 54, 1–78.

    PubMed  CAS  Google Scholar 

  3. Hirano, T., Yasukawa, K., Harada, H., et al. (1986), Nature 324, 73–76.

    Article  PubMed  CAS  Google Scholar 

  4. Ikebuchi, K., Wong, G. G., Clark, S. C., Ihle, J. N., Hirai, Y., and Ogawa, M. (1987), Proc. Natl. Acad. Sci. USA 84, 9035–9039.

    Article  PubMed  CAS  Google Scholar 

  5. Koike, K., Nakahata, T., Takagi, M., et al. (1988), J. Exp. Med. 168, 879–890.

    Article  PubMed  CAS  Google Scholar 

  6. Ishibashi, T., Kimura, H., Shikama, Y., et al. (1989), Blood 74, 1241–1244.

    PubMed  CAS  Google Scholar 

  7. Noma, T., Mizuta, T., Rosen, A., Hirano, T., Kishimoto, T., and Honjo, T. (1987), Immunol. Lett. 15, 249–253.

    Article  PubMed  CAS  Google Scholar 

  8. Okada, M., Kitahara, M., Kishimoto, S., Matsuda, T., Hirano, T., and Kishimoto, T. (1988), J. Immunol. 141, 1543–1549.

    PubMed  CAS  Google Scholar 

  9. Miyaura, C., Onozaki, K., Akiyama, Y., et al. (1988), FEBS Lett. 234, 17–21.

    Article  PubMed  CAS  Google Scholar 

  10. Shabo, Y., Lotem, J., Rubinstein, M., et al. (1988), Blood 72, 2070–2073.

    PubMed  CAS  Google Scholar 

  11. Gauldie, J., Richards, C., Harnish, D., Lansdorp, P., and Baumann, H. (1987), Proc. Natl. Acad. Sci. USA 84, 7251–7255.

    Article  PubMed  CAS  Google Scholar 

  12. Andus, T., Geiger, T., Hirano, T., et al. (1987), FEBS Lett. 221, 18–22.

    Article  PubMed  CAS  Google Scholar 

  13. Castell, J. V., Gomez-Lechon, M. J., David, M., Hirano, T., Kishimoto, T., and Heinrich, P. C. (1988), FEBS Lett. 232, 347–350.

    Article  PubMed  CAS  Google Scholar 

  14. Ulich, T. R., del Castillo, J., and Guo, K. Z. (1989), Blood 73, 108–110.

    PubMed  CAS  Google Scholar 

  15. Tamura, T., Udagawa, N., Takahashi, N., et al. (1993), Proc. Natl. Acad. Sci. USA 90, 11,924–11,928.

    CAS  Google Scholar 

  16. Yamasaki, K., Taga, T., Hirata, Y., et al. (1988), Science 241, 825–828.

    Article  PubMed  CAS  Google Scholar 

  17. Taga, T., Hibi, M., Hirata, Y., et al. (1989), Cell 58, 573–581.

    Article  PubMed  CAS  Google Scholar 

  18. Hibi, M., Murakami, M., Saito, M., Hirano, T., Taga, T., and Kishimoto, T. (1990), Cell 63, 1149–1157.

    Article  PubMed  CAS  Google Scholar 

  19. Uson, J., Balsa, A., Pascual-Salcedo, D., et al. (1997), J. Rheumatol. 24, 2069–2075.

    PubMed  CAS  Google Scholar 

  20. Desgeorges, A., Gabay, C., Silacci, P., et al. (1997), J. Rheumatol. 24, 1510–1516.

    PubMed  CAS  Google Scholar 

  21. Sato, K., Tsuchiya, M., Saldanha, J., et al. (1993), Cancer Res. 53, 851–856.

    PubMed  CAS  Google Scholar 

  22. Nishimoto, N., Ogata, A., Shima, Y., et al. (1994), J. Exp. Med. 179, 1343–1347.

    Article  PubMed  CAS  Google Scholar 

  23. Keller, A. R., Hochholzer, L., and Castleman, B. (1972), Cancer 29, 670–683.

    Article  PubMed  CAS  Google Scholar 

  24. Peterson, B. A. and Frizzera, G. (1993), Semin. Oncol. 20, 636–647.

    PubMed  CAS  Google Scholar 

  25. Yoshizaki, K., Matsuda, T., Nishimoto, N., et al. (1989), Blood 74, 1360–1367.

    PubMed  CAS  Google Scholar 

  26. Beck, J. T., Hsu, S. M., Wijdenes, J., et al. (1994), N. Engl. J. Med. 330, 602–605.

    Article  PubMed  CAS  Google Scholar 

  27. Nishimoto, N., Sasai, M., Shima, Y., et al. (2000), Blood 95, 56–61.

    PubMed  CAS  Google Scholar 

  28. Nishimoto, N., Kanakura, Y., Aozasa, K., et al., Blood in press.

  29. Shanahan, F. (2002), Lancet 359, 62–69.

    Article  PubMed  CAS  Google Scholar 

  30. Targan, S. R., Hanauer, S. B., van Deventer, S. J., et al. (1997), N. Engl. J. Med. 337, 1029–1035.

    Article  PubMed  CAS  Google Scholar 

  31. Hanauer, S. B., Feagan, B. G., Lichtenstein, G. R., et al. (2002), Lancet 359, 1541–1549.

    Article  PubMed  CAS  Google Scholar 

  32. Present, D. H., Rutgeerts, P., Targan, S., et al. (1999), N. Engl. J. Med. 340, 1398–1405.

    Article  PubMed  CAS  Google Scholar 

  33. Mitsuyama, K., Toyonaga, A., Sasaki, E., et al. (1995), Gut 36, 45–49.

    Article  PubMed  CAS  Google Scholar 

  34. Holub, M. C., Mako, E., Devay, T., et al. (1998), Scand. J. Gastroenterol. 228(Suppl.), 47–50.

    CAS  Google Scholar 

  35. Mitsuyama, K., Sasaki, E., Toyonaga, A., et al. (1991), Digestion 50, 104–111.

    Article  PubMed  CAS  Google Scholar 

  36. Kusugami, K., Fukatsu, A., Tanimoto, M., et al. (1995), Dig. Dis. Sci. 40, 949–959.

    Article  PubMed  CAS  Google Scholar 

  37. Arai, F., Takahashi, T., Furukawa, K., Matsushima, K., and Asakura, H. (1998), Dig. Dis. Sci. 43, 2071–2079.

    Article  PubMed  CAS  Google Scholar 

  38. Funakoshi, K., Sugimura, K., Anezaki, K., Bannai, H., Ishizuka, K., and Asakura, H. (1998), Digestion 59, 73–78.

    Article  PubMed  CAS  Google Scholar 

  39. Hosokawa, T., Kusugami, K., Ina, K., et al. (1999), J. Gastroenterol. Hepatol. 14, 987–996.

    Article  PubMed  CAS  Google Scholar 

  40. Atreya, R., Mudter, J., Finotto, S., et al. (2000), Nat. Med. 6, 583–588.

    Article  PubMed  CAS  Google Scholar 

  41. Yamamoto, M., Yoshizaki, K., Kishimoto, T., and Ito, H. (2000), J. Immunol. 164, 4878–4882.

    PubMed  CAS  Google Scholar 

  42. Ito, H., Hirotani T., Yamamoto, M., Ogawa, H., and Kishimoto, T. (2002), J. Gastroenterol. 37(Suppl. 14), 56–61.

    PubMed  CAS  Google Scholar 

  43. Ito, H., Takazoe, M., Fukuda, Y., et al. (2004), Gastroenterology 126, 989–996.

    Article  PubMed  CAS  Google Scholar 

  44. Harris, E. D. Jr. (1990), N. Engl. J. Med. 322, 1277–1289.

    Article  PubMed  Google Scholar 

  45. Hirano, T., Matsuda, T., Turner, M., et al. (1988), Eur. J. Immunol. 18, 1797–1801.

    Article  PubMed  CAS  Google Scholar 

  46. Miyasaka, N., Sato, K., Hashimoto, J., et al. (1989), Clin. Immunol. Immunopatho. 52, 238–247.

    Article  CAS  Google Scholar 

  47. Harigai, M., Hara, M., Kitani, A., et al. (1991), J. Clin. Lab. Immunol. 34, 107–113.

    PubMed  CAS  Google Scholar 

  48. Colville-Nash, P. R. and Scott, D. L. (1992), Ann. Rheum. Dis. 51, 919–925.

    Article  PubMed  CAS  Google Scholar 

  49. Nakahara, H., Song, J., Sugimoto, M., et al. (2003), Arthritis Rheum. 48, 1521–1529.

    Article  PubMed  CAS  Google Scholar 

  50. Houssiau, F. A., Devogelaer, J. P., Van Damme, J., de Deuxchaisnes, C. N., and Van Snick, J. (1988), Arthritis Rheum. 31, 784–788.

    Article  PubMed  CAS  Google Scholar 

  51. Sack, U., Kinne, R. W., Marx, T., Heppt, P., Bender, S., and Emmrich, F. (1993), Rheumatol. Int. 13, 45–51.

    Article  PubMed  CAS  Google Scholar 

  52. Madhok, R., Crilly, A., Watson, J., and Capell, H. A. (1993), Ann. Rheum. Dis. 52, 232–234.

    PubMed  CAS  Google Scholar 

  53. Wendling, D., Racadot, E., and Wijdenes, J. (1993), J. Rheumatol. 20, 259–262.

    PubMed  CAS  Google Scholar 

  54. Alonzi, T., Fattori, E., Lazzaro, D., et al. (1998), J. Exp. Med. 187, 461–468.

    Article  PubMed  CAS  Google Scholar 

  55. Sasai, M., Saeki, Y., Ohshima, S., et al. (1999), Arthritis Rheum. 42, 1635–1643.

    Article  PubMed  CAS  Google Scholar 

  56. Takagi, N., Mihara, M., Moriya, Y., et al. (1998), Arthritis Rheum. 41, 2117–2121.

    Article  PubMed  CAS  Google Scholar 

  57. Mihara, M., Kotoh, M., Nishimoto, N., et al. (2001), Clin. Immunol. 98, 319–326.

    Article  PubMed  CAS  Google Scholar 

  58. Matsuno, H., Sawai, T., Nezuka, T., et al. (1998), Arthritis Rheum. 41, 2014–2021.

    Article  PubMed  CAS  Google Scholar 

  59. Nishimoto, N., Kishimoto, T., and Yoshizaki, K. (2000), Ann. Rheum. Dis. 59, i21-i27.

    Article  PubMed  CAS  Google Scholar 

  60. Choy, E. H., Isenberg, D. A., Garrood, T., et al. (2002), Arthritis Rheum. 46, 3143–3150.

    Article  PubMed  CAS  Google Scholar 

  61. Nishimoto, N., Yoshizaki, K., Maeda, K., et al. (2003), J. Rheumatol. 30, 1426–1435.

    PubMed  CAS  Google Scholar 

  62. Nishimoto, N., Yoshizaki, K., Miyasaka, N., et al. (2004), Arthritis Rheum. 50, 1761–1769.

    Article  PubMed  CAS  Google Scholar 

  63. Maini, R. N., Taylor, P. C., Pavelka, K., et al. (2003), Arthritis Rheum. 48(Suppl), S652, 1704.

Download references

Author information

Authors and Affiliations

  1. Laboratory of Immune Regulation, Graduate School of Frontier Biosciences, Osaka University, Japan

    Norihiro Nishimoto

Authors
  1. Norihiro Nishimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Norihiro Nishimoto.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nishimoto, N. Clinical studies in patients with Castleman’s disease, Crohn’s disease, and rheumatoid arthritis in Japan. Clinic Rev Allerg Immunol 28, 221–229 (2005). https://doi.org/10.1385/CRIAI:28:3:221

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1385/CRIAI:28:3:221

Index Entries

Search

Navigation