tetano
Editor, Senior Moderator
J Innate Immun
. 2022 May 11;1-14.
doi: 10.1159/000524560. Online ahead of print.
IL-1 Mediates Tissue-Specific Inflammation and Severe Respiratory Failure in COVID-19
Georgios Renieris[SUP] 1 [/SUP], Eleni Karakike[SUP] 1 [/SUP], Theologia Gkavogianni[SUP] 1 [/SUP], Dionysia-Eirini Droggiti[SUP] 1 [/SUP], Emmanouil Stylianakis[SUP] 1 [/SUP], Theano Andriopoulou[SUP] 1 [/SUP], Victoria-Marina Spanou[SUP] 1 [/SUP], Dionyssios Kafousopoulos[SUP] 1 [/SUP], Mihai G Netea[SUP] 2 3 [/SUP], Jesper Eugen-Olsen[SUP] 4 [/SUP], John Simard[SUP] 5 [/SUP], Evangelos J Giamarellos-Bourboulis[SUP] 1 [/SUP]
Affiliations
Abstract
Acute respiratory distress syndrome (ARDS) in COVID-19 has been associated with catastrophic inflammation. We present measurements in humans and a new animal model implicating a role in danger-associated molecular patterns. Calprotectin (S100A8/A9) and high-mobility group box 1 (HMGB1) were measured in patients without/with ARDS, and admission calprotectin was associated with soluble urokinase plasminogen activator receptor (suPAR). An animal model was developed by intravenous injection of plasma from healthy or patients with COVID-19 ARDS into C57/BL6 mice once daily for 3 consecutive days. Mice were treated with one anti-S100A8/A9 antibody, the IL-1 receptor antagonist anakinra or vehicle, and Flo1-2a anti-murine anti-IL-1α monoclonal antibody or the specific antihuman IL-1α antibody XB2001 or isotype controls. Cytokines and myeloperoxidase (MPO) were measured in tissues. Calprotectin, but not HMGB1, was elevated in ARDS. Higher suPAR indicated higher calprotectin. Animal challenge with COVID-19 plasma led to inflammatory reactions in murine lung and intestines as evidenced by increased levels of TNFα, IL-6, IFNγ, and MPO. Lung inflammation was attenuated with anti-S100A8/A9 pre-treatment. Anakinra treatment restored these levels. Similar decrease was found in mice treated with Flo1-2a but not with XB2001. Circulating alarmins, specifically calprotectin, of critically ill COVID-19 patients induces tissue-specific inflammatory responses through an IL-1-mediated mechanism. This could be attenuated through inhibition of IL-1 receptor or of IL-1α.
Keywords: Acute respiratory distress syndrome; Calprotectin; Coronavirus diseases 2019; Interleukin-1; Interleukin-6; Severe respiratory failure; Soluble urokinase plasminogen activator receptor; Tumor necrosis factor.
. 2022 May 11;1-14.
doi: 10.1159/000524560. Online ahead of print.
IL-1 Mediates Tissue-Specific Inflammation and Severe Respiratory Failure in COVID-19
Georgios Renieris[SUP] 1 [/SUP], Eleni Karakike[SUP] 1 [/SUP], Theologia Gkavogianni[SUP] 1 [/SUP], Dionysia-Eirini Droggiti[SUP] 1 [/SUP], Emmanouil Stylianakis[SUP] 1 [/SUP], Theano Andriopoulou[SUP] 1 [/SUP], Victoria-Marina Spanou[SUP] 1 [/SUP], Dionyssios Kafousopoulos[SUP] 1 [/SUP], Mihai G Netea[SUP] 2 3 [/SUP], Jesper Eugen-Olsen[SUP] 4 [/SUP], John Simard[SUP] 5 [/SUP], Evangelos J Giamarellos-Bourboulis[SUP] 1 [/SUP]
Affiliations
- PMID: 35545011
- DOI: 10.1159/000524560
Abstract
Acute respiratory distress syndrome (ARDS) in COVID-19 has been associated with catastrophic inflammation. We present measurements in humans and a new animal model implicating a role in danger-associated molecular patterns. Calprotectin (S100A8/A9) and high-mobility group box 1 (HMGB1) were measured in patients without/with ARDS, and admission calprotectin was associated with soluble urokinase plasminogen activator receptor (suPAR). An animal model was developed by intravenous injection of plasma from healthy or patients with COVID-19 ARDS into C57/BL6 mice once daily for 3 consecutive days. Mice were treated with one anti-S100A8/A9 antibody, the IL-1 receptor antagonist anakinra or vehicle, and Flo1-2a anti-murine anti-IL-1α monoclonal antibody or the specific antihuman IL-1α antibody XB2001 or isotype controls. Cytokines and myeloperoxidase (MPO) were measured in tissues. Calprotectin, but not HMGB1, was elevated in ARDS. Higher suPAR indicated higher calprotectin. Animal challenge with COVID-19 plasma led to inflammatory reactions in murine lung and intestines as evidenced by increased levels of TNFα, IL-6, IFNγ, and MPO. Lung inflammation was attenuated with anti-S100A8/A9 pre-treatment. Anakinra treatment restored these levels. Similar decrease was found in mice treated with Flo1-2a but not with XB2001. Circulating alarmins, specifically calprotectin, of critically ill COVID-19 patients induces tissue-specific inflammatory responses through an IL-1-mediated mechanism. This could be attenuated through inhibition of IL-1 receptor or of IL-1α.
Keywords: Acute respiratory distress syndrome; Calprotectin; Coronavirus diseases 2019; Interleukin-1; Interleukin-6; Severe respiratory failure; Soluble urokinase plasminogen activator receptor; Tumor necrosis factor.