Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients
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.
Mots clés
- Hematoxylin
- Eosin and Saffron ELISA
- Enzyme-linked Immunosorbent assay TNF-a
- Tumor necrosis factor-a DAD
- Diffuse Alveolar Damage PBMC
- Peripheral Blood Mononuclear Cells ACE
- Angiotensin-Converting Enzyme ORF3
- Open reading frame RNA
- Ribonucleic acid Ab
- Absent-In-Melanoma-2 ASC
- antibody PANapotosis
- Reverse Transcriptase Polymerase Chain Reaction HES
- Acute-Respiratory-Distress-Syndrome RT-PCR
- Invasive Mechanical Ventilation ARDS
- Intensive Care Unit IMV
- Extracorporeal Membrane Oxygenation ICU
- Immunoglobin G ECMO
- Cluster Differenciation IgG
- Caspase Recruitment Domain CD
- Apoptosis-associated speck-like protein CARD
- Nuclear factor kappa-lightchain NACTH
- High-mobility group box 1
- Apoptosis-associated speck-like protein
- Absent-In-Melanoma-2
- pyrin domain containing 3
- Pyrin Domain
- Leucine-Rich Repeat
- HET-E et TEP1 NTPases implicated in apoptosis and MHC transcription activation"
- Nuclear factor kappa-lightchain
- Acute-respiratory-distress-syndrome
- Tumor necrosis factor receptor 1
- Interleukin-Receptor antagonist
- Pyrosis
- Chemokines
- interferon-gamma
- Interleukin
- Bronchoalveolar lavage fluids
- Pathogen-associated molecular patterns
- Danger-associated molecular patterns
- Coronavirus Disease-2019
- Necroptosis
- Apoptosis
- Enzyme-linked Immunosorbent assay
- acute respiratory distress syndrome
- PANapotosis
- antibody
- Ab
- Ribonucleic acid
- Open reading frame
- Angiotensin-Converting Enzyme
- Peripheral Blood Mononuclear Cells
- Diffuse Alveolar Damage
- Tumor necrosis factor-a
- vasculopathy
- Eosin and Saffron
- Reverse Transcriptase Polymerase Chain Reaction
- Acute-Respiratory-Distress-Syndrome
- Invasive Mechanical Ventilation
- Intensive Care Unit
- Extracorporeal Membrane Oxygenation
- Immunoglobin G
- Cluster Differenciation
- Caspase Recruitment Domain
- interferon-gamma CXCL-
- NOD-like receptor family
- Pyrin Domain NLRP3
- Leucine-Rich Repeat PYD
- HET-E et TEP1 NTPases implicated in apoptosis and MHC transcription activation" LRR
- Acute-respiratory-distress-syndrome NF-kB
- Tumor necrosis factor receptor 1 ARDS
- Interleukin-Receptor antagonist TNFR-1
- High-mobility group box 1 Il-1Ra
- Chemokines HMGB1
- pyrin domain containing 3 AIM2
- Interleukin IFN-g
- Bronchoalveolar lavage fluids IL-
- Pathogen-associated molecular patterns BALF
- Danger-associated molecular patterns PAMPS
- Coronavirus Disease-2019 DAMPS
- COVID-19 COVID
- bronchoalveolar fluid
- cytokines
- caspase-1
Domaines
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