Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19.

Autor:	Rodríguez-Hernández MÁ; Area of Liver, Digestive and Inflammatory Diseases, Institute of Biomedicine of Seville (IBIS), Spanish National Research Council (CSIC) - University of Seville (US) - Virgen del Rocio University Hospital (HUVR), Seville, Spain., Carneros D; Area of Liver, Digestive and Inflammatory Diseases, Institute of Biomedicine of Seville (IBIS), Spanish National Research Council (CSIC) - University of Seville (US) - Virgen del Rocio University Hospital (HUVR), Seville, Spain., Núñez-Núñez M; Department of Pharmacy, San Cecilio University Hospital, Granada, Spain.; Infectious Disease Unit, San Cecilio University Hospital, Granada, Spain.; Biosanitary Research Institute of Granada (ibs.Granada), Granada, Spain., Coca R; Department of Clinical Analysis, Virgen de las Nieves University Hospital, Granada, Spain., Baena R; Department of Pharmaceutical Technology and Chemistry, University of Navarra, Pamplona, Spain., López-Ruiz GM; Area of Liver, Digestive and Inflammatory Diseases, Institute of Biomedicine of Seville (IBIS), Spanish National Research Council (CSIC) - University of Seville (US) - Virgen del Rocio University Hospital (HUVR), Seville, Spain., Cano-Serrano ME; Department of Anaesthesiology, San Cecilio University Hospital, Granada, Spain., Martínez-Tellería A; Department of Anaesthesiology, Virgen de las Nieves University Hospital, Granada, Spain., Fuentes-López A; Department of Microbiology, San Cecilio University Hospital, Granada, Spain., Praena-Fernandez JM; Department of Statistics, Science Faculty, University of Granada, Granada, Spain., Garbers C; Department of Pathology, Medical Faculty, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany., Hernández-Quero J; Infectious Disease Unit, San Cecilio University Hospital, Granada, Spain., García F; Biosanitary Research Institute of Granada (ibs.Granada), Granada, Spain.; Department of Microbiology, San Cecilio University Hospital, Granada, Spain.; Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), ISCIII, Madrid, Spain., Rose-John S; Institute of Biochemistry, Kiel University, Kiel, Germany., Bustos M; Area of Liver, Digestive and Inflammatory Diseases, Institute of Biomedicine of Seville (IBIS), Spanish National Research Council (CSIC) - University of Seville (US) - Virgen del Rocio University Hospital (HUVR), Seville, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 May 13; Vol. 13, pp. 891456. Date of Electronic Publication: 2022 May 13 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.891456
Abstrakt:	IL-6 is one of the major mediators of the hyper-inflammatory responses with complex biological functions as it can signal via different modes of action. IL-6 by classical signalling has anti-inflammatory and antibacterial activities, while trans-signalling mediates pro-inflammatory effects. The net biological effect of IL-6 is established by multiple factors beyond its absolute concentration. Here, we assess the relationship between IL-6 signalling variables [IL-6, soluble IL-6R (sIL-6R) and soluble gp130 (sgp130)] and outcomes in a cohort of 366 COVID-19 patients. The potential trans-signalling was evaluated by a ratio between the pro-inflammatory binary IL-6:sIL-6R complex and the inactive ternary IL-6:sIL-6R:sgp130 complex (binary/ternary complex) and the fold molar excess of sgp130 over sIL-6R (FME). Our data provide new evidence that high levels of IL-6, sIL-6R, sgp130, binary/ternary complex ratio, and low FME are independent predictors of COVID-19 severity in survivor patients (without death), and the combination of IL-6 + sIL-6R + sgp130 exhibited the most robust classification capacity. Conversely, in a subgroup of patients with a very poor prognosis, we found that high levels of IL-6 and low levels of sIL-6R, sgp130, and binary/ternary complex ratio were predictors of death. In this context, the highest predictive capacity corresponded to the combined analysis of IL-6 + FME + lymphopenia + creatinine. Herein, we present IL-6 signalling variables as a helpful tool for the early identification and stratification of patients with clear implications for treatment and clinical decision-making. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Rodríguez-Hernández, Carneros, Núñez-Núñez, Coca, Baena, López-Ruiz, Cano-Serrano, Martínez-Tellería, Fuentes-López, Praena-Fernandez, Garbers, Hernández-Quero, García, Rose-John and Bustos.)
Databáze:	MEDLINE
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