Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Sep 28:14:1255533.
doi: 10.3389/fimmu.2023.1255533. eCollection 2023.

Interleukin 6: at the interface of human health and disease

Elena Grebenciucova  1 , Stephen VanHaerents  1
Affiliations
Review

Interleukin 6: at the interface of human health and disease

Elena Grebenciucova et al. Front Immunol. .

Abstract

Interleukin 6 (IL-6) is a pleiotropic cytokine executing a diverse number of functions, ranging from its effects on acute phase reactant pathways, B and T lymphocytes, blood brain barrier permeability, synovial inflammation, hematopoiesis, and embryonic development. This cytokine empowers the transition between innate and adaptive immune responses and helps recruit macrophages and lymphocytes to the sites of injury or infection. Given that IL-6 is involved both in the immune homeostasis and pathogenesis of several autoimmune diseases, research into therapeutic modulation of IL-6 axis resulted in the approval of a number of effective treatments for several autoimmune disorders like neuromyelitis optica spectrum disorder (NMOSD), rheumatoid arthritis, juvenile idiopathic arthritis, polyarticular juvenile idiopathic arthritis, giant cell arteritis (GCA), and cytokine release syndrome, associated with SARS-CoV2 pneumonia. This review discusses downstream inflammatory pathways of IL-6 expression and therapeutic applications of IL-6 blockade, currently investigated for the treatment of several other autoimmune conditions such as autoimmune encephalitis, autoimmune epilepsy, as well as myelin oligodendrocyte glycoprotein associated demyelination (MOGAD). This review further highlights the need for clinical trials to evaluate IL-6 blockade in disorders such neuropsychiatric lupus erythematosus (SLE), sarcoidosis and Behcet's.

Keywords: IL-6; NMOSD; NPSLE; cytokine; interleukin 6; neuro-inflammation; sartralizumab; tocilizumab.

PubMed Disclaimer

Conflict of interest statement

EG has served on advisory boards and received honoraria from Horizon Therapeutics, Alexion, Genentech, Prevail Therapeutics and has received research support from NIH and Genentech. SV declares that his spouse is an employee of Abbvie.

References

    1. Kishimoto T, Ishizaka K. Regulation of antibody response in vitro. X. Biphasic effect of cyclic AMP on the secondary anti-hapten antibody response to anti-immunoglobulin and enhancing soluble factor. J Immunol (1976) 116(2):534–41. doi: 10.4049/jimmunol.116.2.534 - DOI - PubMed
    1. Sehgal PB, Grieninger G, Tosato G. Regulation of the acute phase and immune responses: interleukin-6. Ann N Y Acad Sci (1989) 557:1–583. - PubMed
    1. Scheller J, Garbers C, Rose-John S. Interleukin-6: from basic biology to selective blockade of pro-inflammatory activities. Semin Immunol (2014) 26(1):2–12. doi: 10.1016/j.smim.2013.11.002 - DOI - PubMed
    1. Hunter CA, Jones SA. IL-6 as a keystone cytokine in health and disease. Nat Immunol (2015) 16:448–57. doi: 10.1038/ni.3153 - DOI - PubMed
    1. Kamimura D, Ishihara K, Hirano T. IL-6 signal transduction and its physiological roles: the signal orchestration model. Rev Physiol Biochem Pharmacol (2003) 149:1–38. doi: 10.1007/s10254-003-0012-2 - DOI - PubMed