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1. Interleukin-22 mitigates acute respiratory distress syndrome (ARDS).

Author

Sharven Taghavi, Olan Jackson-Weaver, Sarah Abdullah, Alanna Wanek, Robert Drury, Jacob Packer, Aaron Cotton-Betteridge, Juan Duchesne, Derek Pociask, and Jay Kolls

Subjects
Medicine, Science
Abstract

BackgroundThe goal of this study was to determine if IL-22:Fc would Acute Respiratory Distress Syndrome (ARDS).Summary background dataNo therapies exist for ARDS and treatment is purely supportive. Interleukin-22 (IL-22) plays an integral component in recovery of the lung from infection. IL-22:Fc is a recombinant protein with a human FC immunoglobulin that increases the half-life of IL-22.Study designARDS was induced in C57BL/6 mice with intra-tracheal lipopolysaccharide (LPS) at a dose of 33.3 or 100 ug. In the low-dose LPS group (LDG), IL-22:FC was administered via tail vein injection at 30 minutes (n = 9) and compared to sham (n = 9). In the high-dose LPS group (HDG), IL-22:FC was administered (n = 11) then compared to sham (n = 8). Euthanasia occurred after bronchioalveolar lavage (BAL) on post-injury day 4.ResultsIn the LDG, IL-22:FC resulted in decreased protein leak (0.15 vs. 0.25 ug/uL, p = 0.02). BAL protein in animals receiving IL-22:Fc in the HDG was not different. For the HDG, animals receiving IL-22:Fc had lower BAL cell counts (539,636 vs 3,147,556 cells/uL, p = 0.02). For the HDG, IL-6 (110.6 vs. 527.1 pg/mL, p = 0.04), TNF-α (5.87 vs. 25.41 pg/mL, p = 0.04), and G-CSF (95.14 vs. 659.6, p = 0.01) levels were lower in the BAL fluid of IL-22:Fc treated animals compared to sham.ConclusionsIL-22:Fc decreases lung inflammation and lung capillary leak in ARDS. IL-22:Fc may be a novel therapy for ARDS.

Published
2021
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2. Interleukin-22 mitigates acute respiratory distress syndrome (ARDS)

Author

Juan Duchesne, Sarah Abdullah, Sharven Taghavi, Robert Drury, Jacob Packer, Alanna Wanek, Jay K. Kolls, Aaron Cotton-Betteridge, Olan Jackson-Weaver, and Derek Pociask

Subjects
Lipopolysaccharides, Male, ARDS, Critical Care and Emergency Medicine, Lipopolysaccharide, Pulmonology, Neutrophils, Cancer Treatment, Gastroenterology, Biochemistry, Interleukin 22, Capillary leak, chemistry.chemical_compound, Mice, White Blood Cells, Medical Conditions, Animal Cells, Medicine and Health Sciences, Medicine, Lymphocytes, Immune Response, Acute Respiratory Distress Syndrome, Respiratory Distress Syndrome, Multidisciplinary, biology, Lung Injury, Animal Models, Recombinant Proteins, medicine.anatomical_structure, Oncology, Experimental Organism Systems, Tumor necrosis factor alpha, Female, medicine.symptom, Antibody, Cellular Types, Bronchoalveolar Lavage Fluid, Research Article, medicine.medical_specialty, Science, Immune Cells, Immunology, Cell Enumeration Techniques, Inflammation, Cytokine Therapy, Mouse Models, Respiratory Mucosa, Glycocalyx, Research and Analysis Methods, Respiratory Disorders, Signs and Symptoms, Model Organisms, Respiratory Failure, Internal medicine, Animals, Lymphocyte Count, Lung, Blood Cells, business.industry, Interleukins, Macrophages, Biology and Life Sciences, Proteins, Pneumonia, Receptors, Interleukin, Cell Biology, medicine.disease, Immunoglobulin Fc Fragments, Mice, Inbred C57BL, chemistry, biology.protein, Animal Studies, Clinical Medicine, business, Collagens
Abstract

Background The goal of this study was to determine if IL-22:Fc would Acute Respiratory Distress Syndrome (ARDS). Summary background data No therapies exist for ARDS and treatment is purely supportive. Interleukin-22 (IL-22) plays an integral component in recovery of the lung from infection. IL-22:Fc is a recombinant protein with a human FC immunoglobulin that increases the half-life of IL-22. Study design ARDS was induced in C57BL/6 mice with intra-tracheal lipopolysaccharide (LPS) at a dose of 33.3 or 100 ug. In the low-dose LPS group (LDG), IL-22:FC was administered via tail vein injection at 30 minutes (n = 9) and compared to sham (n = 9). In the high-dose LPS group (HDG), IL-22:FC was administered (n = 11) then compared to sham (n = 8). Euthanasia occurred after bronchioalveolar lavage (BAL) on post-injury day 4. Results In the LDG, IL-22:FC resulted in decreased protein leak (0.15 vs. 0.25 ug/uL, p = 0.02). BAL protein in animals receiving IL-22:Fc in the HDG was not different. For the HDG, animals receiving IL-22:Fc had lower BAL cell counts (539,636 vs 3,147,556 cells/uL, p = 0.02). For the HDG, IL-6 (110.6 vs. 527.1 pg/mL, p = 0.04), TNF-α (5.87 vs. 25.41 pg/mL, p = 0.04), and G-CSF (95.14 vs. 659.6, p = 0.01) levels were lower in the BAL fluid of IL-22:Fc treated animals compared to sham. Conclusions IL-22:Fc decreases lung inflammation and lung capillary leak in ARDS. IL-22:Fc may be a novel therapy for ARDS.

Published
2021

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