ArticleAmerican journal of respiratory cell and molecular biology2012
Postinfection A77-1726 treatment improves cardiopulmonary function in H1N1 influenza-infected mice.
Article in American journal of respiratory cell and molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 23 citations in OpenAlex.
- Adenosine Triphosphate Release From Influenza-Infected Lungs Enhances Neutrophil Activation and Promotes Disease Progression.The Journal of infectious diseases · 2024Article
- Effects of Purinergic Receptor Deletion or Pharmacologic Modulation on Pulmonary Inflammation in Mice.ACS pharmacology & translational science · 2022Article
- Cytidine 5'-Diphosphocholine Corrects Alveolar Type II Cell Mitochondrial Dysfunction in Influenza-infected Mice.American journal of respiratory cell and molecular biology · 2022Article
- Postexposure Liponucleotide Prophylaxis and Treatment Attenuates Acute Respiratory Distress Syndrome in Influenza-infected Mice.American journal of respiratory cell and molecular biology · 2021Article
- Article
- Adenosine at the Interphase of Hypoxia and Inflammation in Lung Injury.Frontiers in immunology · 2020Review
- DNA repair and genomic stability in lungs affected by acute injury.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2019Review
- Article
- ATP catabolism by tissue nonspecific alkaline phosphatase contributes to development of ARDS in influenza-infected mice.American journal of physiology. Lung cellular and molecular physiology · 2018Article
- Purinergic signalling links mechanical breath profile and alveolar mechanics with the pro-inflammatory innate immune response causing ventilation-induced lung injury.Purinergic signalling · 2017Review
- Article
- Lethal H1N1 influenza A virus infection alters the murine alveolar type II cell surfactant lipidome.American journal of physiology. Lung cellular and molecular physiology · 2016Article
- Ecto-5'-nucleotidase CD73 modulates the innate immune response to influenza infection but is not required for development of influenza-induced acute lung injury.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- TGF-β-induced IL-6 prevents development of acute lung injury in influenza A virus-infected F508del CFTR-heterozygous mice.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Selective targeting of alveolar type II respiratory epithelial cells by anti-surfactant protein-C antibody-conjugated lipoplexes.Journal of controlled release : official journal of the Controlled Release Society · 2015Article
- Infection of mice with influenza A/WSN/33 (H1N1) virus alters alveolar type II cell phenotype.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Activation of A1-adenosine receptors promotes leukocyte recruitment to the lung and attenuates acute lung injury in mice infected with influenza A/WSN/33 (H1N1) virus.Journal of virology · 2014Article
- Heterozygosity for the F508del mutation in the cystic fibrosis transmembrane conductance regulator anion channel attenuates influenza severity.The Journal of infectious diseases · 2013Article
- Influenza A H1N1 induces declines in alveolar gas exchange in mice consistent with rapid post-infection progression from acute lung injury to ARDS.Influenza and other respiratory viruses · 2013Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Acute respiratory disease is associated with significant morbidity and mortality in influenza. Because antiviral drugs are only effective early in infection, new agents are needed to treat nonvaccinated patients presenting with late-stage disease, particularly those who develop acute respiratory distress syndrome. We found previously that the de novo pyrimidine synthesis inhibitor A77-1726 reversed the influenza-induced impairment of alveolar fluid clearance. Patients with acute respiratory distress syndrome and intact alveolar fluid clearance demonstrate lower mortality than those with compromised fluid clearance. We therefore investigated the effects of treatment with nebulized A77-1726 (67.5 mg/kg) on indices of cardiopulmonary function relevant to the diagnosis of acute respiratory distress syndrome. BALB/cAnNCr mice (8-12 wk old) were inoculated intranasally with 10,000 plaque-forming units/mouse influenza A/WSN/33 (H1N1). Pulse oximetry was performed daily. Alveolar fluid clearance, lung water, and lung mechanics were measured at 2 and 6 days after inoculation in live, ventilated mice by BSA instillation, magnetic resonance imaging, and forced-oscillation techniques, respectively. A77-1726 treatment at 1 day after inoculation delayed mortality. Treatment on Days 1 or 5 reduced viral replication on Day 6, and improved alveolar fluid clearance, peripheral oxygenation, and cardiac function. Nebulized A77-1726 also reversed influenza-induced increases in lung water content and volume, improved pulmonary mechanics, reduced bronchoalveolar lavage fluid ATP and neutrophil content, and increased IL-6 concentrations. The ability of A77-1726 to improve cardiopulmonary function in influenza-infected mice and to reduce the severity of ongoing acute respiratory distress syndrome late in infection suggests that pyrimidine synthesis inhibitors are promising therapeutic candidates for the management of severe influenza.
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