» Articles » PMID: 33872590

Interleukin-6: Obstacles to Targeting a Complex Cytokine in Critical Illness

Overview
Publisher Elsevier
Specialty Pulmonary Medicine
Date 2021 Apr 19
PMID 33872590
Citations 84
Authors
Affiliations
Soon will be listed here.
Abstract

Circulating concentrations of the pleiotropic cytokine interleukin-6 (IL-6) are known to be increased in pro-inflammatory critical care syndromes, such as sepsis and acute respiratory distress syndrome. Elevations in serum IL-6 concentrations in patients with severe COVID-19 have led to renewed interest in the cytokine as a therapeutic target. However, although the pro-inflammatory properties of IL-6 are widely known, the cytokine also has a series of important physiological and anti-inflammatory functions. An adequate understanding of the complex processes by which IL-6 signalling occurs is crucial for the correct interpretation of IL-6 concentrations in the blood or lung, the use of IL-6 as a critical care biomarker, or the design of effective anti-IL-6 strategies. Here, we outline the role of IL-6 in health and disease, explain the different types of IL-6 signalling and their contribution to the net biological effect of the cytokine, describe the approaches to IL-6 inhibition that are currently available, and discuss implications for the future use of treatments such as tocilizumab in the critical care setting.

Citing Articles

Targeting sepsis through inflammation and oxidative metabolism.

Jacob S, Jacob S, Thoppil J World J Crit Care Med. 2025; 14(1):101499.

PMID: 40060738 PMC: 11671842. DOI: 10.5492/wjccm.v14.i1.101499.


Advances in Interleukin-6 Family Cytokines and the Role in Respiratory Diseases.

Ji T, Huang G, Cao Y, Gao Y, Gao X J Inflamm Res. 2025; 18:3125-3141.

PMID: 40059944 PMC: 11889408. DOI: 10.2147/JIR.S508031.


Laminarin Alleviates Acute Lung Injury Induced by LPS Through Inhibition of M1 Macrophage Polarisation.

Zeng L, Zhang J, Song R, Dong X, Wei Z, Li X J Cell Mol Med. 2025; 29(5):e70440.

PMID: 40045157 PMC: 11882389. DOI: 10.1111/jcmm.70440.


T-2 toxin-induced splenic injury by disrupting the gut microbiota-spleen axis via promoting IL-6/JAK/STAT1 signaling-mediated inflammation and apoptosis and its mitigation by elemental nano-selenium.

Liu M, Li X, Sun H, Yan Y, Xia Z, Refaie A Arch Toxicol. 2025; .

PMID: 40014112 DOI: 10.1007/s00204-025-04005-3.


Inflammatory Response and Anti-Inflammatory Treatment in Persistent Inflammation-Immunosuppression-Catabolism Syndrome (PICS).

Xiong D, Geng H, Lv X, Wang S, Jia L J Inflamm Res. 2025; 18:2267-2281.

PMID: 39968098 PMC: 11834740. DOI: 10.2147/JIR.S504694.


References
1.
Veiga V, Prats J, Farias D, Rosa R, Dourado L, Zampieri F . Effect of tocilizumab on clinical outcomes at 15 days in patients with severe or critical coronavirus disease 2019: randomised controlled trial. BMJ. 2021; 372:n84. PMC: 7815251. DOI: 10.1136/bmj.n84. View

2.
Matheson N, Wong P, Schuyler M, Travis J . Interaction of human alpha-1-proteinase inhibitor with neutrophil myeloperoxidase. Biochemistry. 1981; 20(2):331-6. DOI: 10.1021/bi00505a016. View

3.
Pierce C, Preston-Hurlburt P, Dai Y, Aschner C, Cheshenko N, Galen B . Immune responses to SARS-CoV-2 infection in hospitalized pediatric and adult patients. Sci Transl Med. 2020; 12(564). PMC: 7658796. DOI: 10.1126/scitranslmed.abd5487. View

4.
DORING G . The role of neutrophil elastase in chronic inflammation. Am J Respir Crit Care Med. 1994; 150(6 Pt 2):S114-7. DOI: 10.1164/ajrccm/150.6_Pt_2.S114. View

5.
OShea J, Gadina M, Schreiber R . Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell. 2002; 109 Suppl:S121-31. DOI: 10.1016/s0092-8674(02)00701-8. View