Interleukin 6 in rheumatic diseases


Authors: H. Mann
Authors‘ workplace: Revmatologický ústav, Praha
Published in: Čes. Revmatol., 17, 2009, No. 1, p. 30-35.
Category: Overview Reports

Overview

Interleukin 6 is a pleiotropic cytokine, which has an impact on various cell lines through a unique mechanism of signal transmission and significantly participates in the regulation of immune response. IL-6 has an important role in the etiopathogenesis of inflammatory rheumatic diseases. The IL-6 blocking via tocilizumab – a humanized monoclonal antibody against IL-6R – has proved its efficacy in the treatment of rheumatoid arthritis and juvenile idiopathic arthritis with systemic onset.

Key words:
Interleukin 6, signal transmission, tocilizumab, rheumatoid arthritis, SOJIA


Sources

1. Kishimoto T. Interleukin-6: discovery of a pleiotropic cytokine. Arthritis Res Ther. 2006;8 Suppl 2: S2.

2. Muraguchi A, Kishimoto T, Miki T, et al. T cell-replacing factor (TRF)-induced IgG secretion in human B blastoid cell line and demonstration of acceptors for TRF. J Immunol 1981; 127: 412–416.

3. Hirano T, Matsuda T, Hosoi K, et al. Absence of antiviral activity in recombinant B cell stimulatory factor 2 (BSF-2). Immunol Lett 1988; 17: 41–45.

4. Müllberg J, Schooltink H, Stoyan T, et al. The soluble interleukin-6 receptor is generated by shedding. Eur J Immunol 1993; 23: 794–800.

5. Horiuchi S, Koyanagi Y, Zhou Y, et al. Soluble interleukin-6 receptors released from T cell of granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism. Eur J Immunol 1994; 24: 1945–1948.

6. Peters M, Müller A, Rose-John S. Interleukin-6 and soluble interleukin-6 receptor: direct stimulation of gp130 and hematopoesis. Blood 1998; 92: 3495–3504.

7. Romano M, Sironi M, Toniatti C, et al. Role of IL-6 and its soluble receptor in induction of chemokines and leukocyte recruitment. Immunity 1997; 6: 315–325.

8. Gabay C, Smith MF, Eidlen D, et al. Interleukin 1 receptor antagonist (IL-1Ra) is an acute-phase protein J Clin Invest 1997; 99: 2930–2940.

9. Bettelli E, Carrier Y, Gao W, et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 2006; 441: 235–238.

10. Kattah MG, Wong MT, Yocum MD, et al. Cytokines secreted in response to Toll-like receptor ligand stimulation modulate differentiation of human Th17 cells.Arthritis Rheum 2008; 58: 1619–29.

11. Nishimoto N. Interleukin-6 in rheumatoid arthritis. Curr Opin Rheumatol 2006; 18: 277–281.

12. de Benedetti F, Martini A. Targeting the interleukin-6 receptor: a new treatment for systemic juvenile idiopathic arthritis? Arthritis Rheum 2005; 52: 687–93.

13. Tackey E, Lipsky PE, Illei GG. Rationale for interleukin-6 blockade in systemic lupus erythematosus. Lupus 2004; 13: 339–43.

14. Lu ZY, Brailly H, Wijdenes J, et al. Measurement of whole body interleukin-6 (IL-6) production: prediction of the efficacy of anti-IL-6 treatments. Blood 1995; 86: 3123–31.

15. Wendling D, Racadot E, Wijdenes J. Treatment of severe rheumatoid arthritis by anti-interleukin 6 monoclonal antibody. J Rheumatol 1993; 20: 259–62.

16. Montero-Julian FA, Klein B, Gautherot E, et al. Pharmacokinetic study of anti-interleukin-6 (IL-6) therapy with monoclonal antibodies: enhancement of IL-6 clearance by cocktails of anti-IL-6 antibodies. Blood 1995; 85: 917–24.

17. De Benedetti F, Vivarelli M, Pignatti P, et al. In vivo neutralization of human IL-6 (hIL-6) achieved by immunization of hIL-6-transgenic mice with a hIL-6 receptor antagonist. J Immunol 2001; 166: 4334–40.

18. Rose-John S, Waetzig GH, Scheller J, et al. The IL-6/sIL-6R complex as a novel target for therapeutic approaches. Expert Opin Ther Targets. 2007; 11: 613–24.

19. Su JL, Lai KP, Chen CA, et al. A novel peptide specifically binding to interleukin-6 receptor (gp80) inhibits angiogenesis and tumor growth. Cancer Res 2005; 65: 4827–35.

20. www.fda.gov/ohrms/dockets/ac/acmenu.htm

21. Smolen JS, Beaulieu A, Rubbert-Roth A, et al. Effect of interleukin-6 receptor inhibition with tocilizumab in patients with rheumatoid arthritis: a double-blind, placebo-controlled, randomised trial. Lancet 2008; 371: 987–97.

22. Genovese MC, McKay JD, Nasonov EL, et al. Interleukin-6 receptor inhibition with tocilizumab reduces disease activity in rheumatoid arthritis with inadequate response to disease-modifying antirheumatic drugs: the tocilizumab in combination with traditional disease-modifying antirheumatic drug therapy study. Arthritis Rheum 2008; 58: 2968–80.

23. Emery P, Keystone E, Tony HP, et al. IL-6 receptor inhibition with tocilizumab improves treatment outcomes in patients with rheumatoid arthritis refractory to anti-tumour necrosis factor biologicals: results from a 24-week multicentre randomised placebo-controlled trial. Ann Rheum Dis 2008; 67: 1516–23.

24. Jones G, Gu JR, Lowenstein M, et al. Tocilizumab Monotherapy is Superior to Methotrexate Monotherapy in Reducing Disease Activity in Patients with Rheumatoid Arthritis. Ann Rheum Dis 2008; 67: 89.

25. Kremer JM, Fleischmann RM, Halland AM. Tocilizumab Inhibits Structural Joint Damage in Rheumatoid Arthritis Patients with an Inadequate Response to Methotrexate. Abstract L14 ACR 2008.

26. Woo P, et al. Open label phase II trial of single, ascending doses of MRA in Caucasian children with severe systemic juvenile idiopathic arthritis: proof of principle of the efficacy of IL-6 receptor blockade in this type of arthritis and demonstration of prolonged clinical improvement. Arthritis Res Ther 2005; 7: 1281–8.

27. Yokota S, et al. Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 2005; 52: 818–25.

28. Yokota S, et al. Efficacy and safety of tocilizumab in patients with systemic-onset juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled, withdrawal phase III trial. Lancet 2008; 371: 998–1006.

29. Iwamoto M, et al. Humanized monoclonal anti-interleukin-6 receptor antibody for treatment of intractable adult-onset Still‘s disease. Arthritis Rheum 2002; 46: 3388–3389

30. Nakahara H, et al..A case report of a patient with refractory adult-onset Still‘s disease who was successfully treated with tocilizumab over 6 years. Mod Rheumatol 2008 E pub ahead of print

31. Smolen JS, Beaulieu AD, Dikranian A, et al. Safety of Tocilizumab in Patients with Rheumatoid Arthritis: Pooled Analysis of Five Phase 3 Clinical Trials Arthritis Rheum 2008; 58: S784.

Labels
Dermatology & STDs Paediatric rheumatology Rheumatology
Login
Forgotten password

Don‘t have an account?  Create new account

Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account