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Resolvin E1-Chemerin receptor 1 axis is dysregulated in critical COVID-19 patients
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Orientador(es)
Resumo(s)
Resolvin E1 (RvE1) and Resolvin D1 (RvD1) are key resolvins implicated in inflammation resolution of respiratory and infectious diseases. In contrast to cytokines, they have been scarcely explored in COVID-19 and their ability for discriminating COVID-19 severity and patient outcomes has not been compared with that of cytokines. Therefore, among a panel comprising cytokines (interleukin (IL)-1beta, IL-6, IL-10, tumor necrosis factor alpha, interferon gamma and granulocyte-macrophage colony-stimulating factor), RvD1 and RvE1 and their respective receptors (FPR2, Chemerin1), we evaluated which mediators better distinguished COVID-19 severity, the need of mechanical ventilation and patient mortality.
Blood was collected from 61 patients with “severe” (n = 27), “critical” (n = 17) and “critical on veno-venous extracorporeal membrane oxygenation (VV-ECMO)” (n = 17) COVID-19 at admission, days 3–4 and days 5–8, and from controls (n = 23) at a single time point. We measured cytokines by multiplex immunoassays, resolvins by enzyme-linked immunosorbent assays, and FPR2 and Chemerin1 mRNA by real-time quantitative polymerase chain reaction.
We obtained principal component analysis (PCA)/partial least squares discriminant analysis (PLS-DA) models significantly differentiating (P < 0.001): controls from each patient group; “severe” from all critical patients; patients without or with mechanical ventilation, and survivors from non-survivors. RvE1 consistently showed a variable importance in projection (VIP) score > 2.5 and a p(corr) >0.8, being the most relevant discriminating variable. Univariate and repeated measures multivariate analyses showed higher RvE1 in “critical on VV-ECMO”, mechanically ventilated patients and non-survivors, while Chemerin1 exhibited an opposite profile. RvE1 positively correlated with inflammation and partial pressure of CO2, whereas Chemerin1 correlated with lower inflammation, better respiratory function and lower hospital length of stay.
We conclude that RvE1 was the mediator best distinguishing COVID-19 severity and that RvE1-Chemerin1 axis is dysregulated in this disease.
Highlights: -Serum RvE1 distinguishes COVID-19 severity better than proinflammatory cytokines. -Critical on VV-ECMO COVID-19 patients have higher serum RvE1 and lower Chemerin1 mRNA. -Mechanically ventilated patients have higher serum RvE1 and lower Chemerin1 mRNA. -COVID-19 mortality is associated with higher serum RvE1 and lower Chemerin1 mRNA. -Serum RvE1 and Chemerin1 mRNA correlate with lung function in COVID-19 patients.
Highlights: -Serum RvE1 distinguishes COVID-19 severity better than proinflammatory cytokines. -Critical on VV-ECMO COVID-19 patients have higher serum RvE1 and lower Chemerin1 mRNA. -Mechanically ventilated patients have higher serum RvE1 and lower Chemerin1 mRNA. -COVID-19 mortality is associated with higher serum RvE1 and lower Chemerin1 mRNA. -Serum RvE1 and Chemerin1 mRNA correlate with lung function in COVID-19 patients.
Descrição
Palavras-chave
COVID-19 Chemerin Receptor 1 Cytokines Inflammation Resolution Resolvin E1 VV-ECMO Resolvin E1-Chemerin
Contexto Educativo
Citação
Int Immunopharmacol. 2025 Dec 10:167:115669. doi: 10.1016/j.intimp.2025.115669. Epub 2025 Oct 12
Editora
Elsevier