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
. 2021 Mar;21(3):263.
doi: 10.3892/etm.2021.9693. Epub 2021 Jan 25.

Multifactorial expression of IL-6 with update on COVID-19 and the therapeutic strategies of its blockade (Review)

Elena Niculet  1 , Valentin Chioncel  2   3 , Alina M Elisei  4   5 , Magdalena Miulescu  1 , Olimpia D Buzia  4   5 , Lawrence C Nwabudike  6 , Mihaela Craescu  1 , Miruna Draganescu  7 , Florin Bujoreanu  8 , Elisabeta Marinescu  4 , Manuela Arbune  9 , Diana Sabina Radaschin  5 , Carmen Bobeica  10 , Aurel Nechita  1   11 , Alin L Tatu  5   7   8
Affiliations
Review

Multifactorial expression of IL-6 with update on COVID-19 and the therapeutic strategies of its blockade (Review)

Elena Niculet et al. Exp Ther Med. 2021 Mar.

Abstract

Interleukin 6 (IL-6), a cytokine produced by various cells of the human body (macrophages, lymphocytes, astrocytes, ischemic myocytes, endothelial cells) has both pro-inflammatory and anti-inflammatory properties, being a key component in regulating various physiologic and pathological processes. The structure of this molecule and the receptor system it possesses are important due to the different activities that IL-6 can exert; through trans-signaling pro-inflammatory activities are mediated, while through classic signaling, IL-6 is responsible for anti-inflammatory and regenerative activities. IL-6 signaling is involved in coronary artery disease and the global COVID-19 pandemic. This proatherogenic cytokine reaches elevated serum levels in the cytokine storm generated by SARS-CoV-2, and is also associated with smoking or obesity-classic cardiovascular risk factors which promote inflammatory states. IL-6 levels are proportionally correlated with dyslipidemia, hypertension and glucose dysregulation, and they are associated with poor outcomes in patients with unstable angina or acute myocardial infarction. IL-6 targeting for treatment development (not only) in cardiovascular disease and COVID-19 is still a matter of ongoing research, although tocilizumab has proven to be effective in reducing the proatherogenic effects of IL-6 and is suggested to improve COVID-19 patient survival.

Keywords: COVID-19; IL-6; arthritis; cardiovascular; inflammation; interleukin-6; receptor; signaling pathway; tocilizumab.

PubMed Disclaimer

References

    1. Coughlin BA, Trombley BT, Mohr S. Interleukin-6 (IL-6) mediates protection against glucose toxicity in human Müller cells via activation of VEGF-A signaling. Biochem Biophys Res Commun. 2019;517:227–232. doi: 10.1016/j.bbrc.2019.07.044. - DOI - PubMed
    1. Matthes AT, Manfroi B, Huard B. Revisiting IL-6 antagonism in multiple myeloma. Crit Rev Oncol Hematol. 2016;105:1–4. doi: 10.1016/j.critrevonc.2016.07.006. - DOI - PubMed
    1. Rizzo MD, Crawford RB, Bach A, Sermet S, Amalfitano A, Kaminski NE. Imiquimod and interferon-alpha augment monocyte-mediated astrocyte secretion of MCP-1, IL-6 and IP-10 in a human co-culture system. J Neuroimmunol. 2019;333(576969) doi: 10.1016/j.jneuroim.2019.576969. - DOI - PMC - PubMed
    1. Niu X, Chen Y, Qi L, Liang G, Wang Y, Zhang L, Qu Y, Wang W. Hypoxia regulates angeogenic-osteogenic coupling process via up-regulating IL-6 and IL-8 in human osteoblastic cells through hypoxia-inducible factor-1α pathway. Cytokine. 2019;113:117–127. doi: 10.1016/j.cyto.2018.06.022. - DOI - PubMed
    1. Kaur S, Bansal Y, Kumar R, Bansal G. A panoramic review of IL-6: Structure, pathophysiological roles and inhibitors. Bioorg Med Chem. 2020;28(115327) doi: 10.1016/j.bmc.2020.115327. - DOI - PubMed

LinkOut - more resources