@misc{10481/75480,
year = {2022},
month = {5},
url = {http://hdl.handle.net/10481/75480},
abstract = {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.},
organization = {Spanish Institute of
Health Carlos III (COV-20/00792)},
organization = {European
Commission - NextgenerationEU (Regulation EU 2020/2094)},
organization = {CSIC's Global Health Platform (PTI Salud Global)},
organization = {Spanish Institute of
Health Carlos III and the European Commission -
NextgenerationEU (Regulation EU 2020/2094)},
organization = {iPFIS (IFI 19/00048) funded by Spanish Institute of
Health Carlos III},
organization = {Rio Hortega
contract (CM20/00074)},
publisher = {Frontiers},
keywords = {COVID-19},
keywords = {IL-6},
keywords = {Soluble receptors},
keywords = {Soluble IL-6 receptor (sIL-6R)},
keywords = {Soluble gp130 (sgp130)},
keywords = {IL-6 trans-signalling},
title = {Identification of IL-6 Signalling Components as Predictors of Severity and Outcome in COVID-19},
doi = {10.3389/fimmu.2022.891456},
author = {Rodríguez Hernández, María Ángeles and Núñez Núñez, María and Coca, Ramón and Cano Serrano, María Elena and Martínez Tellería, Alberto and Fuentes López, Ana and Praena Fernández, Juan Manuel and Hernández Quero, José and García García, Federico},
}