Factors of Interleukin-6 Signaling in COVID-19 Patients with Lung Damage of Varying Degrees: A Pilot Study

Overview

Journal Bull Exp Biol Med

Publisher Springer

Specialty General Medicine

Date 2024 Jun 18

PMID 38890212

Authors

A A Korotaeva

E V Samoilova

N V Pogosova

D T Kuchiev

N V Gomyranova

F N Paleev

Affiliations

Soon will be listed here.

Abstract

Specific features of IL-6 signal transduction were studied in 89 patients with lung damage of varying degrees during the first COVID-19 pandemic wave. The levels of IL-6 signaling components (IL-6, sIL-6R, and sgp130) and highly sensitive C-reactive protein (hsCRP) were examined in patients with intact lungs (CT-0), mild (CT-1), moderate (CT-2), moderate to severe (CT-3), and severe (CT-4) lung damage. Seventy patients were re-examined 3-7 months after discharge from the hospital. The IL-6 and hsCRP levels increased several times with severing lung damage severity. In patients with CT-3, sIL6-R increased statistically significantly and remained high in CT-4 patients. sgp130 levels were lower in CT-1 and CT-2 patients and higher in CT-3 and CT-4 patients compared to CT-0 patients. We revealed a positive correlation between IL-6 and hsCRP levels in CT-1, CT-2, and CT-3 patients. In CT-3 patients, sIL-6R levels positively correlated with IL-6 concentration. The studied parameters decreased considerably in all patients 3-7 months after discharge. It can be suggested that IL-6 classic-signaling is predominant in CT-1 and CT-2, while trans-signaling prevails in CT-3. Disorders in regulatory mechanisms of IL-6 signaling occur in CT-4, which prevents physiological elimination of IL-6 hyperactivity. The results obtained are preliminary and require a broader study.

Citing Articles

Cytokine Storm in COVID-19: Exploring IL-6 Signaling and Cytokine-Microbiome Interactions as Emerging Therapeutic Approaches.

Paranga T, Mitu I, Pavel-Tanasa M, Rosu M, Miftode I, Constantinescu D Int J Mol Sci. 2024; 25(21).

PMID: 39518964 PMC: 11547016. DOI: 10.3390/ijms252111411.

References

Batah S, Fabro A . Pulmonary pathology of ARDS in COVID-19: A pathological review for clinicians. Respir Med. 2020; 176:106239. PMC: 7674971. DOI: 10.1016/j.rmed.2020.106239. View

Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C . Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020; 8(4):420-422. PMC: 7164771. DOI: 10.1016/S2213-2600(20)30076-X. View

Boechat J, Chora I, Morais A, Delgado L . The immune response to SARS-CoV-2 and COVID-19 immunopathology - Current perspectives. Pulmonology. 2021; 27(5):423-437. PMC: 8040543. DOI: 10.1016/j.pulmoe.2021.03.008. View

Jamoussi A, Messaoud L, Jarraya F, Rachdi E, Ben Mrad N, Yaalaoui S . Interleukin6 prediction of mortality in critically ill COVID19 patients: A prospective observational cohort study. PLoS One. 2023; 18(3):e0279935. PMC: 9977034. DOI: 10.1371/journal.pone.0279935. View

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. PMC: 3491447. DOI: 10.7150/ijbs.4989. View

Jostock T, Mullberg J, Ozbek S, Atreya R, Blinn G, Voltz N . Soluble gp130 is the natural inhibitor of soluble interleukin-6 receptor transsignaling responses. Eur J Biochem. 2000; 268(1):160-7. DOI: 10.1046/j.1432-1327.2001.01867.x. View

Scheller J, Garbers C, Rose-John S . Interleukin-6: from basic biology to selective blockade of pro-inflammatory activities. Semin Immunol. 2013; 26(1):2-12. DOI: 10.1016/j.smim.2013.11.002. View

Koutsakos M, Rowntree L, Hensen L, Chua B, van de Sandt C, Habel J . Integrated immune dynamics define correlates of COVID-19 severity and antibody responses. Cell Rep Med. 2021; 2(3):100208. PMC: 7862905. DOI: 10.1016/j.xcrm.2021.100208. View

Tanaka T, Narazaki M, Kishimoto T . IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014; 6(10):a016295. PMC: 4176007. DOI: 10.1101/cshperspect.a016295. View

10.

Sproston N, Ashworth J . Role of C-Reactive Protein at Sites of Inflammation and Infection. Front Immunol. 2018; 9:754. PMC: 5908901. DOI: 10.3389/fimmu.2018.00754. View

11.

Jones S, Horiuchi S, Topley N, Yamamoto N, Fuller G . The soluble interleukin 6 receptor: mechanisms of production and implications in disease. FASEB J. 2001; 15(1):43-58. DOI: 10.1096/fj.99-1003rev. View

12.

Ziegler L, Lundstrom A, Havervall S, Thalin C, Gigante B . IL-6 signalling biomarkers in hospitalised patients with moderate to severe SARS-CoV-2 infection in a single centre study in Sweden. Cytokine. 2022; 159:156020. PMC: 9420722. DOI: 10.1016/j.cyto.2022.156020. View

13.

Lokau J, Garbers C . Biological functions and therapeutic opportunities of soluble cytokine receptors. Cytokine Growth Factor Rev. 2020; 55:94-108. DOI: 10.1016/j.cytogfr.2020.04.003. View

14.

Schumertl T, Lokau J, Rose-John S, Garbers C . Function and proteolytic generation of the soluble interleukin-6 receptor in health and disease. Biochim Biophys Acta Mol Cell Res. 2021; 1869(1):119143. DOI: 10.1016/j.bbamcr.2021.119143. View

15.

Rodriguez-Hernandez M, Carneros D, Nunez-Nunez M, Coca R, Baena R, Lopez-Ruiz G . Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19. Front Immunol. 2022; 13:891456. PMC: 9137400. DOI: 10.3389/fimmu.2022.891456. View