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IL-6 as a keystone cytokine in health and disease

A Corrigendum to this article was published on 18 October 2017

This article has been updated

Abstract

Interleukin 6 (IL-6) has a broad effect on cells of the immune system and those not of the immune system and often displays hormone-like characteristics that affect homeostatic processes. IL-6 has context-dependent pro- and anti-inflammatory properties and is now regarded as a prominent target for clinical intervention. However, the signaling cassette that controls the activity of IL-6 is complicated, and distinct intervention strategies can inhibit this pathway. Clinical experience with antagonists of IL-6 has raised new questions about how and when to block this cytokine to improve disease outcome and patient wellbeing. Here we discuss the effect of IL-6 on innate and adaptive immunity and the possible advantages of various antagonists of IL-6 and consider how the immunobiology of IL-6 may inform clinical decisions.

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Figure 1: Two distinct modes of IL-6 receptor signaling.

Debbie Maizels/Nature Publishing Group

Figure 2: IL-6 control of B cells and humoral immunity.

Debbie Maizels/Nature Publishing Group

Figure 3: Effect of IL-6 on T cell activities.

Debbie Maizels/Nature Publishing Group

Figure 4: Therapeutic targeting of IL-6 and its receptor.

Debbie Maizels/Nature Publishing Group

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Change history

  • 17 August 2017

    In the version of this article initially published, some of the labels in Figure 4a,b were incorrect. In Figure 4a, in the group of IL-6 blockers (top right), 'ALX-0061' should be removed and 'Siltuximab' and 'MEDI 5117' should be added, and in the group of IL-6R blockers (middle right), 'Siltuximab' and 'ALD518' should be removed and 'ALX-0061' should be added. In Figure 4b, in the group of inhibitors at bottom left, 'MEDI 5517' should be revised to 'MEDI 5117'. These errors have been corrected in the HTML and PDF versions of the article.

  • 18 October 2017

    Nat. Immunol. 16, 448–457 (2015); published online 21 April 2015; corrected after print 17 August 2017 In the version of this article initially published, some of the labels in Figure 4a,b were incorrect. In Figure 4a, in the group of IL-6 blockers (top right), 'ALX-0061' should be removed and 'Siltuximab' and 'MEDI 5117' should be added, and in the group of IL-6R blockers (middle right), 'Siltuximab' and 'ALD518' should be removed and 'ALX-0061' should be added.

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Correspondence to Christopher A Hunter or Simon A Jones.

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S.A.J. has received funding support from Hoffman-La Roche, Ferring Pharmaceuticals and NovImmune and during the past 5 years has acted as an advisory consultant for Roche, Chugai Pharmaceuticals, NovImmune, Genentech, Sanofi Regeneron, Johnson & Johnson, Janssen Pharmaceuticals, Eleven Biotherapeutics and UCB. C.A.H. has received support from Amgen, Johnson & Johnson, and Janssen Pharmaceuticals, has acted as an advisory consultant for Medimmune and Biogen and is a member of the scientific advisory board of Surface Oncology.

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Hunter, C., Jones, S. IL-6 as a keystone cytokine in health and disease. Nat Immunol 16, 448–457 (2015). https://doi.org/10.1038/ni.3153

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