Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19
Metadatos
Afficher la notice complèteAuteur
Rodríguez Hernández, María Ángeles; Núñez Núñez, María; Coca, Ramón; Cano Serrano, María Elena; Martínez Tellería, Alberto; Fuentes López, Ana; Praena Fernández, Juan Manuel; Hernández Quero, José; García García, FedericoEditorial
Frontiers
Materia
COVID-19 IL-6 Soluble receptors Soluble IL-6 receptor (sIL-6R) Soluble gp130 (sgp130) IL-6 trans-signalling
Date
2022-05-13Referencia bibliográfica
Rodríguez-Hernández MÁ... [et al.] (2022) Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19. Front. Immunol. 13:891456. doi: [10.3389/fimmu.2022.891456]
Patrocinador
Spanish Institute of Health Carlos III (COV-20/00792); European Commission - NextgenerationEU (Regulation EU 2020/2094); CSIC's Global Health Platform (PTI Salud Global); Spanish Institute of Health Carlos III and the European Commission - NextgenerationEU (Regulation EU 2020/2094); iPFIS (IFI 19/00048) funded by Spanish Institute of Health Carlos III; Rio Hortega contract (CM20/00074)Résumé
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 proinflammatory
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.