Schett G. Physiological effects of modulating the interleukin-6 axis. Rheumatology (Oxford). 2018;57(Suppl_2):ii43–50.
Article CAS PubMed Google Scholar
Bethin KE, Vogt SK, Muglia LJ. Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation. Proc Natl Acad Sci USA. 2000;97(16):9317–22.
Article CAS PubMed PubMed Central Google Scholar
Kraakman MJ, Kammoun HL, Allen TL, Deswaerte V, Henstridge DC, Estevez E, et al. Blocking IL-6 trans-signaling prevents high-fat diet-induced adipose tissue macrophage recruitment but does not improve insulin resistance. Cell Metabol. 2015;21(3):403–16.
Schett G, Elewaut D, McInnes IB, Dayer JM, Neurath MF. How cytokine networks fuel inflammation: toward a cytokine-based disease taxonomy. Nat Med. 2013;19(7):822–4.
Article CAS PubMed Google Scholar
Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol. 2015;16(5):448–57.
Article CAS PubMed Google Scholar
Rose-John S, Winthrop K, Calabrese L. The role of IL-6 in host defence against infections: immunobiology and clinical implications. Nat Rev Rheumatol. 2017;13(7):399–409.
Article CAS PubMed Google Scholar
Spencer S, Kostel Bal S, Egner W, Lango Allen H, Raza SI, Ma CA, et al. Loss of the interleukin-6 receptor causes immunodeficiency, atopy, and abnormal inflammatory responses. J Exp Med. 2019;216(9):1986–98.
Article CAS PubMed PubMed Central Google Scholar
Mullberg J, Schooltink H, Stoyan T, Gunther M, Graeve L, Buse G, et al. The soluble interleukin-6 receptor is generated by shedding. Eur J Immunol. 1993;23(2):473–80.
Article CAS PubMed Google Scholar
Jostock T, Mullberg J, Ozbek S, Atreya R, Blinn G, Voltz N, et al. Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur J Biochem. 2001;268(1):160–7.
Article CAS PubMed Google Scholar
Nowell MA, Williams AS, Carty SA, Scheller J, Hayes AJ, Jones GW, et al. Therapeutic targeting of IL-6 trans signaling counteracts STAT3 control of experimental inflammatory arthritis. J Immunol. 2009;182(1):613–22.
Article CAS PubMed Google Scholar
Nowell MA, Richards PJ, Horiuchi S, Yamamoto N, Rose-John S, Topley N, et al. Soluble IL-6 receptor governs IL-6 activity in experimental arthritis: blockade of arthritis severity by soluble glycoprotein 130. J Immunol. 2003;171(6):3202–9.
Article CAS PubMed Google Scholar
Sodenkamp J, Waetzig GH, Scheller J, Seegert D, Grotzinger J, Rose-John S, et al. Therapeutic targeting of interleukin-6 trans-signaling does not affect the outcome of experimental tuberculosis. Immunobiology. 2012;217(10):996–1004.
Article CAS PubMed Google Scholar
Hoge J, Yan I, Janner N, Schumacher V, Chalaris A, Steinmetz OM, et al. IL-6 controls the innate immune response against Listeria monocytogenes via classical IL-6 signaling. J Immunol. 2013;190(2):703–11.
Article CAS PubMed Google Scholar
Schreiber S, Aden K, Bernardes JP, Conrad C, Tran F, Hoper H, et al. Therapeutic interleukin-6 trans-signaling inhibition by olamkicept (sgp130Fc) in patients with active inflammatory bowel disease. Gastroenterology. 2021;160(7):2354-66.e11.
Article CAS PubMed Google Scholar
Heink S, Yogev N, Garbers C, Herwerth M, Aly L, Gasperi C, et al. Trans-presentation of IL-6 by dendritic cells is required for the priming of pathogenic T(H)17 cells. Nat Immunol. 2017;18(1):74–85.
Article CAS PubMed Google Scholar
Narazaki M, Kishimoto T. Current status and prospects of IL-6-targeting therapy. Expert Rev Clin Pharmacol. 2022;15(5):575–92.
Article CAS PubMed Google Scholar
US FDA. Sarilumab approval for polymyalgia rheumatica. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761037s013lbl.pdf. Accessed 2 July 2023.
US FDA. Tocilizumab approval for systemic sclerosis-induced interstitial lung disease. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/125276s131lbl.pdf. Accessed 9 July 2023.
Schaper F, Rose-John S. Interleukin-6: biology, signaling and strategies of blockade. Cytokine Growth Factor Rev. 2015;26(5):475–87.
Article CAS PubMed Google Scholar
Rose-John S. IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci. 2012;8(9):1237–47.
Article CAS PubMed PubMed Central Google Scholar
Lazzerini PE, Capecchi PL, Guidelli GM, Selvi E, Acampa M, Laghi-Pasini F. Spotlight on sirukumab for the treatment of rheumatoid arthritis: the evidence to date. Drug Design Dev Ther. 2016;10:3083–98.
Robak T, Gladalska A, Stepien H, Robak E. Serum levels of interleukin-6 type cytokines and soluble interleukin-6 receptor in patients with rheumatoid arthritis. Mediators Inflamm. 1998;7(5):347–53.
Article CAS PubMed PubMed Central Google Scholar
Zhang M, Bai Y, Wang Y, Cui H, Tang M, Wang L, et al. Cumulative evidence for associations between genetic variants in interleukin 6 receptor gene and human diseases and phenotypes. Front Immunol. 2022;13: 860703.
Article CAS PubMed PubMed Central Google Scholar
Avci AB, Feist E, Burmester GR. Targeting IL-6 or IL-6 receptor in rheumatoid arthritis: what’s the difference? BioDrugs. 2018;32(6):531–46.
Article CAS PubMed Google Scholar
Olokizumab official approval. Available from: https://grls.rosminzdrav.ru/GRLS.aspx?RegNumber=&MnnR=%d0%9e%d0%bb%d0%be%d0%ba%d0%b8%d0%b7%d1%83%d0%bc%d0%b0%d0%b1&lf=&TradeNmR=&OwnerName=&MnfOrg=&MnfOrgCountry=&isfs=0®type=1%2c6&pageSize=10&order=Registered&orderType=desc&pageNum=1. Accessed 7 July 2023.
Nasonov E, Fatenejad S, Feist E, Ivanova M, Korneva E, Krechikova DG, et al. Olokizumab, a monoclonal antibody against interleukin 6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by methotrexate: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022;81(4):469–79.
Article CAS PubMed Google Scholar
Feist E, Fatenejad S, Grishin S, Korneva E, Luggen ME, Nasonov E, et al. Olokizumab, a monoclonal antibody against interleukin-6, in combination with methotrexate in patients with rheumatoid arthritis inadequately controlled by tumour necrosis factor inhibitor therapy: efficacy and safety results of a randomised controlled phase III study. Ann Rheum Dis. 2022;81(12):1661–8.
Article CAS PubMed Google Scholar
Smolen JS, Feist E, Fatenejad S, Grishin SA, Korneva EV, Nasonov EL, et al. Olokizumab versus placebo or adalimumab in rheumatoid arthritis. N Engl J Med. 2022;387(8):715–26.
Article CAS PubMed Google Scholar
Feist E, Nasonov E, Luggen M, Fatenejad S, Grishin S, Samsonov M, et al. Long-term safety and efficacy of olokizumab in patients with rheumatoid arthritis: results of an open-label extension study [abstract]. Arthritis Rheumatol. 2022;74(Suppl. 9).
Takeuchi T, Yamanaka H, Harigai M, Tamamura R, Kato Y, Ukyo Y, et al. Sirukumab in rheumatoid arthritis refractory to sulfasalazine or methotrexate: a randomized phase 3 safety and efficacy study in Japanese patients. Arthritis Res Ther. 2018;20(1):42.
Article PubMed PubMed Central Google Scholar
Takeuchi T, Thorne C, Karpouzas G, Sheng S, Xu W, Rao R, et al. Sirukumab for rheumatoid arthritis: the phase III SIRROUND-D study. Ann Rheum Dis. 2017;76(12):2001–8.
Article CAS PubMed Google Scholar
Aletaha D, Bingham CO 3rd, Tanaka Y, Agarwal P, Kurrasch R, Tak PP, et al. Efficacy and safety of sirukumab in patients with active rheumatoid arthritis refractory to anti-TNF therapy (SIRROUND-T): a randomised, double-blind, placebo-controlled, parallel-group, multinational, phase 3 study. Lancet. 2017;389(10075):1206–17.
Article CAS PubMed Google Scholar
Aletaha D, Bingham CO, Karpouzas GA, Takeuchi T, Thorne C, Bili A, et al. Long-term safety and efficacy of sirukumab for patients with rheumatoid arthritis who previously received sirukumab in randomised controlled trials (SIRROUND-LTE). RMD Open. 2021;7(1): e001465.
Article PubMed PubMed Central Google Scholar
Genovese MC, Rubbert-Roth A, Smolen JS, Kremer J, Khraishi M, Gomez-Reino J, et al. Longterm safety and efficacy of tocilizumab in patients with rheumatoid arthritis: a cumulative analysis of up to 4.6 years of exposure. J Rheumatol. 2013;40(6):768–80.
Article CAS PubMed Google Scholar
Fleischmann R, Genovese MC, Lin Y, St John G, van der Heijde D, Wang S, et al. Long-term safety of sarilumab in rheumatoid arthritis: an integrated analysis with up to 7 years’ follow-up. Rheumatology (Oxford). 2020;59(2):292–302.
Article CAS PubMed Google Scholar
Mease P, Strand V, Shalamberidze L, Dimic A, Raskina T, Xu LA, et al. A phase II, double-blind, randomised, placebo-controlled study of BMS945429 (ALD518) in patients with rheumatoid arthritis with an inadequate response to methotrexate. Ann Rheum Dis. 2012;71(7):1183–9.
Article CAS PubMed Google Scholar
Zhao Q, Pang J, Shuster D, Hung C, Baglino S, Dodge R, et al. Anti-IL-6 antibody clazakizumab is more potent than tocilizumab in blocking in vitro and ex vivo IL-6-induced functions (abstract). Arthritis Rheum. 2013;65(Suppl):S1020.
Comments (0)