Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients
RationaleCOVID-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 compare...
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Frontiers Media S.A.
2025-01-01
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| author | Audrey Cambon Christophe Guervilly Christophe Guervilly Clémence Delteil Nicola Potere Richard Bachelier Edwige Tellier Evelyne Abdili Evelyne Abdili Marine Leprince Marco Giani Ildo Polidoro Valentina Albanese Paolo Ferrante Laurence Coffin Michael Schiffrin Laurent Arnaud Romaric Lacroix Romaric Lacroix Sandrine Roque Jean-Marie Forel Jean-Marie Forel Sami Hraiech Sami Hraiech Laurent Daniel Laurent Papazian Françoise Dignat-George Françoise Dignat-George Gilles Kaplanski Gilles Kaplanski |
| author_facet | Audrey Cambon Christophe Guervilly Christophe Guervilly Clémence Delteil Nicola Potere Richard Bachelier Edwige Tellier Evelyne Abdili Evelyne Abdili Marine Leprince Marco Giani Ildo Polidoro Valentina Albanese Paolo Ferrante Laurence Coffin Michael Schiffrin Laurent Arnaud Romaric Lacroix Romaric Lacroix Sandrine Roque Jean-Marie Forel Jean-Marie Forel Sami Hraiech Sami Hraiech Laurent Daniel Laurent Papazian Françoise Dignat-George Françoise Dignat-George Gilles Kaplanski Gilles Kaplanski |
| author_sort | Audrey Cambon |
| collection | DOAJ |
| description | RationaleCOVID-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).ObjectivesTo 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.MethodsHistological 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 resultsTypical “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.ConclusionsIn 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. |
| format | Article |
| id | doaj-art-b8124a6dee394c83bb23c6e1955cd699 |
| institution | DOAJ |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-b8124a6dee394c83bb23c6e1955cd6992025-08-20T02:41:07ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011510.3389/fimmu.2024.14933061493306Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patientsAudrey Cambon0Christophe Guervilly1Christophe Guervilly2Clémence Delteil3Nicola Potere4Richard Bachelier5Edwige Tellier6Evelyne Abdili7Evelyne Abdili8Marine Leprince9Marco Giani10Ildo Polidoro11Valentina Albanese12Paolo Ferrante13Laurence Coffin14Michael Schiffrin15Laurent Arnaud16Romaric Lacroix17Romaric Lacroix18Sandrine Roque19Jean-Marie Forel20Jean-Marie Forel21Sami Hraiech22Sami Hraiech23Laurent Daniel24Laurent Papazian25Françoise Dignat-George26Françoise Dignat-George27Gilles Kaplanski28Gilles Kaplanski29Aix-Marseille Université, INSERM, INRAE, C2VN, Marseille, FranceCentre d’Etudes et de Recherches sur les Services de Santé et qualité de vie EA 3279, Aix-Marseille Université, Marseille, FranceService de Médecine Intensive Réanimation, Hôpital Nord, Assistance Publique- Hôpitaux de Marseille, Chemin des Bourrely, Marseille, FranceDépartement de Médecine légale, Hôpital de la Timone, Assistance Publique-Hôpitaux de Marseille, Marseille University, Marseille, FranceSchool of Medicine and Health Sciences, “G. d’Annunzio” University of Chieti-Pescara, Chieti, ItalyAix-Marseille Université, INSERM, INRAE, C2VN, Marseille, FranceAix-Marseille Université, INSERM, INRAE, C2VN, Marseille, FranceAix-Marseille Université, INSERM, INRAE, C2VN, Marseille, FranceService d’Hématologie et de Biologie vasculaire, CHU La Timone, APHM, Marseille, FranceService de Médecine interne et d’Immunologie clinique, Assistance Publique - Hôpitaux de Marseille, Hôpital La Conception, Marseille, FranceSchool of Medicine and Health Sciences, “G. d’Annunzio” University of Chieti-Pescara, Chieti, ItalyUnit of Legal Medicine, “Santo Spirito” Hospital, Local Health Authority of Pescara, Pescara, ItalyUnit of Legal Medicine, “Santo Spirito” Hospital, Local Health Authority of Pescara, Pescara, ItalyUnit of Legal Medicine, “Santo Spirito” Hospital, Local Health Authority of Pescara, Pescara, ItalyAB2 Bio, Lausanne, SwitzerlandAB2 Bio, Lausanne, SwitzerlandService d’Hématologie et de Biologie vasculaire, CHU La Timone, APHM, Marseille, FranceAix-Marseille Université, INSERM, INRAE, C2VN, Marseille, FranceService d’Hématologie et de Biologie vasculaire, CHU La Timone, APHM, Marseille, FranceService de Médecine interne et d’Immunologie clinique, Assistance Publique - Hôpitaux de Marseille, Hôpital La Conception, Marseille, FranceCentre d’Etudes et de Recherches sur les Services de Santé et qualité de vie EA 3279, Aix-Marseille Université, Marseille, FranceService de Médecine Intensive Réanimation, Hôpital Nord, Assistance Publique- Hôpitaux de Marseille, Chemin des Bourrely, Marseille, FranceCentre d’Etudes et de Recherches sur les Services de Santé et qualité de vie EA 3279, Aix-Marseille Université, Marseille, FranceService de Médecine Intensive Réanimation, Hôpital Nord, Assistance Publique- Hôpitaux de Marseille, Chemin des Bourrely, Marseille, France0Service d’Anatomopathologie, APHM, Aix Marseille University, Marseille, France1Service de Réanimation, Centre Hospitalier de Bastia, Bastia, FranceAix-Marseille Université, INSERM, INRAE, C2VN, Marseille, FranceService d’Hématologie et de Biologie vasculaire, CHU La Timone, APHM, Marseille, FranceAix-Marseille Université, INSERM, INRAE, C2VN, Marseille, FranceService de Médecine interne et d’Immunologie clinique, Assistance Publique - Hôpitaux de Marseille, Hôpital La Conception, Marseille, FranceRationaleCOVID-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).ObjectivesTo 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.MethodsHistological 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 resultsTypical “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.ConclusionsIn 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.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1493306/fullacute respiratory distress syndromevasculopathycaspase-1cytokinesbronchoalveolar fluidCOVID-19 |
| spellingShingle | Audrey Cambon Christophe Guervilly Christophe Guervilly Clémence Delteil Nicola Potere Richard Bachelier Edwige Tellier Evelyne Abdili Evelyne Abdili Marine Leprince Marco Giani Ildo Polidoro Valentina Albanese Paolo Ferrante Laurence Coffin Michael Schiffrin Laurent Arnaud Romaric Lacroix Romaric Lacroix Sandrine Roque Jean-Marie Forel Jean-Marie Forel Sami Hraiech Sami Hraiech Laurent Daniel Laurent Papazian Françoise Dignat-George Françoise Dignat-George Gilles Kaplanski Gilles Kaplanski Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients Frontiers in Immunology acute respiratory distress syndrome vasculopathy caspase-1 cytokines bronchoalveolar fluid COVID-19 |
| title | Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients |
| title_full | Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients |
| title_fullStr | Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients |
| title_full_unstemmed | Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients |
| title_short | Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients |
| title_sort | caspase 1 activation il 1 il 6 signature and ifnγ induced chemokines in lungs of covid 19 patients |
| topic | acute respiratory distress syndrome vasculopathy caspase-1 cytokines bronchoalveolar fluid COVID-19 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1493306/full |
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