tetano
Editor, Senior Moderator
Front Immunol
. 2025 Jan 15:15:1493306.
doi: 10.3389/fimmu.2024.1493306. eCollection 2024. Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients
Audrey Cambon[SUP] 1 [/SUP], Christophe Guervilly[SUP] 2 3 [/SUP], Clémence Delteil[SUP] 4 [/SUP], Nicola Potere[SUP] 5 [/SUP], Richard Bachelier[SUP] 1 [/SUP], Edwige Tellier[SUP] 1 [/SUP], Evelyne Abdili[SUP] 1 6 [/SUP], Marine Leprince[SUP] 7 [/SUP], Marco Giani[SUP] 5 [/SUP], Ildo Polidoro[SUP] 8 [/SUP], Valentina Albanese[SUP] 8 [/SUP], Paolo Ferrante[SUP] 8 [/SUP], Laurence Coffin[SUP] 9 [/SUP], Michael Schiffrin[SUP] 9 [/SUP], Laurent Arnaud[SUP] 6 [/SUP], Romaric Lacroix[SUP] 1 6 [/SUP], Sandrine Roque[SUP] 7 [/SUP], Jean-Marie Forel[SUP] 2 3 [/SUP], Sami Hraiech[SUP] 2 3 [/SUP], Laurent Daniel[SUP] 10 [/SUP], Laurent Papazian[SUP] 11 [/SUP], Françoise Dignat-George[SUP] 1 6 [/SUP], Gilles Kaplanski[SUP] 1 7 [/SUP]
Affiliations
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.
Keywords: COVID-19; acute respiratory distress syndrome; bronchoalveolar fluid; caspase-1; cytokines; vasculopathy.
. 2025 Jan 15:15:1493306.
doi: 10.3389/fimmu.2024.1493306. eCollection 2024. Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients
Audrey Cambon[SUP] 1 [/SUP], Christophe Guervilly[SUP] 2 3 [/SUP], Clémence Delteil[SUP] 4 [/SUP], Nicola Potere[SUP] 5 [/SUP], Richard Bachelier[SUP] 1 [/SUP], Edwige Tellier[SUP] 1 [/SUP], Evelyne Abdili[SUP] 1 6 [/SUP], Marine Leprince[SUP] 7 [/SUP], Marco Giani[SUP] 5 [/SUP], Ildo Polidoro[SUP] 8 [/SUP], Valentina Albanese[SUP] 8 [/SUP], Paolo Ferrante[SUP] 8 [/SUP], Laurence Coffin[SUP] 9 [/SUP], Michael Schiffrin[SUP] 9 [/SUP], Laurent Arnaud[SUP] 6 [/SUP], Romaric Lacroix[SUP] 1 6 [/SUP], Sandrine Roque[SUP] 7 [/SUP], Jean-Marie Forel[SUP] 2 3 [/SUP], Sami Hraiech[SUP] 2 3 [/SUP], Laurent Daniel[SUP] 10 [/SUP], Laurent Papazian[SUP] 11 [/SUP], Françoise Dignat-George[SUP] 1 6 [/SUP], Gilles Kaplanski[SUP] 1 7 [/SUP]
Affiliations
- PMID: 39882243
- PMCID: PMC11774885
- DOI: 10.3389/fimmu.2024.1493306
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.
Keywords: COVID-19; acute respiratory distress syndrome; bronchoalveolar fluid; caspase-1; cytokines; vasculopathy.