ArticleJournal of innate immunity2022
IL-1 Mediates Tissue-Specific Inflammation and Severe Respiratory Failure in COVID-19.
Article in Journal of innate immunity, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed, 33 citations in OpenAlex.
- Molecular pathways driving clarithromycin benefit in community-acquired pneumonia: analysis of the ACCESS randomised trial.EBioMedicine · 2026Trial
- Early treatment of COVID-19 with anakinra guided by soluble urokinase plasminogen receptor plasma levels: a double-blind, randomized controlled phase 3 trial.Nature medicine · 2021Trial
- C6 peptide blockade of Hv1 channels inhibits neutrophil migration into the lungs to suppress Pseudomonas aeruginosa-induced acute lung injury.Respiratory research · 2025Article
- Chain management reduces inflammation (IL-1b, IL-6, IL-8, TNF-a, PCT) and improves vascular (NO, DD, VWF, and ET-1)/immune function in acute respiratory failure: A retrospective cohort study.Journal of medical biochemistry · 2025Article
- Multifaceted Immunomodulatory Nanocomplexes Target Neutrophilic-ROS Inflammation in Acute Lung Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Recent advances of precision immunotherapy in sepsis.Burns & trauma · 2025Review
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- A serum calprotectin lateral flow test as an inflammatory and prognostic marker in acute lung infection: a prospective observational study.ERJ open research · 2024Article
- SARS-CoV-2 and its ORF3a, E and M viroporins activate inflammasome in human macrophages and induce of IL-1α in pulmonary epithelial and endothelial cells.Cell death discovery · 2024Article
- The pathophysiology of sepsis and precision-medicine-based immunotherapy.Nature immunology · 2024Review
- Caspase-1 activation, IL-1/IL-6 signature and IFNγ-induced chemokines in lungs of COVID-19 patients.Frontiers in immunology · 2024Article
- Adjunctive treatment in COVID-19 and sepsis-What did we learn?Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2023Review
- Recombinant SARS-CoV-2 Spike Protein Stimulates Secretion of Chymase, Tryptase, and IL-1β from Human Mast Cells, Augmented by IL-33.International journal of molecular sciences · 2023Article
- A Prospective Cohort Study of COVID-19: Evaluation of the Early Role of IL-1 and IL-6 Antagonists in Improving the Outcome of the Illness and Reduction in the Risk of Death.Healthcare (Basel, Switzerland) · 2023Article
- Efficacy and safety of early soluble urokinase plasminogen receptor plasma-guided anakinra treatment of COVID-19 pneumonia: A subgroup analysis of the SAVE-MORE randomised trial.EClinicalMedicine · 2023Article
- Anakinra authorized to treat severe coronavirus disease 2019; Sepsis breakthrough or time to reflect?Frontiers in microbiology · 2023Article
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- Soluble urokinase Plasminogen Activator Receptor (suPAR) levels are predictive of COVID-19 severity: an Italian experience.Clinical immunology (Orlando, Fla.) · 2022Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.