Article Dans Une Revue Frontiers in Immunology Année : 2025

Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients

Christophe Guervilly
Clémence Delteil
  • Fonction : Auteur
Nicola Potere
  • Fonction : Auteur
Marine Leprince
  • Fonction : Auteur
Marco Giani
  • Fonction : Auteur
Ildo Polidoro
  • Fonction : Auteur
Valentina Albanese
  • Fonction : Auteur
Paolo Ferrante
  • Fonction : Auteur
Laurence Coffin
  • Fonction : Auteur
Michael Schiffrin
  • Fonction : Auteur
Laurent Arnaud
  • Fonction : Auteur
Sandrine Roque
  • Fonction : Auteur
Jean-Marie Forel
Sami Hraiech
Laurent Daniel
  • Fonction : Auteur
Laurent Papazian

Résumé

Rationale COVID-19-associated acute-respiratory distress syndrome (C-ARDS) results from a direct viral injury associated with host excessive innate immune response mainly affecting the lungs. However, cytokine profile in the lung compartment of C-ARDS patients has not been widely studied, nor compared to non-COVID related ARDS (NC-ARDS). Objectives To evaluate caspase-1 activation, IL-1 signature, and other inflammatory cytokine pathways associated with tissue damage using post-mortem lung tissues, bronchoalveolar lavage fluids (BALF), and serum across the spectrum of COVID-19 severity. Methods Histological features were described and activated-caspase-1 labeling was performed in 40 post-mortem biopsies. Inflammatory cytokines were quantified in BALF and serum from 19 steroid-treated-C-ARDSand compared to 19 NC-ARDS. Cytokine concentrations were also measured in serum from 128 COVID-19 patients at different severity stages. Measurements and main results Typical “diffuse alveolar damage” in lung biopsies were associated with activated caspase-1 expression and vascular lesions. Soluble Caspase-1p20, IL-1β, IL-1Ra, IL-6 and at lower level IFNγ and CXCL-10, were highly elevated in BALF from steroid-treated-C-ARDS as well as in NC-ARDS. IL-1β appeared concentrated in BALF, whereas circulating IL-6 and IL-1Ra concentrations were comparable to those in BALF and correlated with severity. TNFα, TNFR1 and CXCL8 however, were significantly higher in NC-ARDS compared to C-ARDS, treated by steroid. Conclusions In the lungs of C-ARDS, both caspase-1 activation with a predominant IL-1β/IL-6 signature and IFNγ -associated chemokines are elevated despite steroid treatment. These pathways may be specifically targeted in ARDS to improve response to treatment and to limit alveolar and vascular lung damage.

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hal-04957423 , version 1 (19-02-2025)

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Audrey Cambon, Christophe Guervilly, Clémence Delteil, Nicola Potere, Richard Bachelier, et al.. Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients. Frontiers in Immunology, 2025, 15, pp.1493306. ⟨10.3389/fimmu.2024.1493306⟩. ⟨hal-04957423⟩
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