Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation
IntroductionThere is an unmet medical need for effective anti-inflammatory agents for the treatment of acute and post-acute lung inflammation caused by respiratory viruses. The semi-synthetic polysaccharide, Pentosan polysulfate sodium (PPS), an inhibitor of NF-kB activation, was investigated for it...
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1030879/full |
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| author | Ravi Krishnan Catherine J. M. Stapledon Helen Mostafavi Helen Mostafavi Helen Mostafavi Joseph R. Freitas Joseph R. Freitas Joseph R. Freitas Xiang Liu Xiang Liu Xiang Liu Suresh Mahalingam Suresh Mahalingam Suresh Mahalingam Ali Zaid Ali Zaid Ali Zaid |
| author_facet | Ravi Krishnan Catherine J. M. Stapledon Helen Mostafavi Helen Mostafavi Helen Mostafavi Joseph R. Freitas Joseph R. Freitas Joseph R. Freitas Xiang Liu Xiang Liu Xiang Liu Suresh Mahalingam Suresh Mahalingam Suresh Mahalingam Ali Zaid Ali Zaid Ali Zaid |
| author_sort | Ravi Krishnan |
| collection | DOAJ |
| description | IntroductionThere is an unmet medical need for effective anti-inflammatory agents for the treatment of acute and post-acute lung inflammation caused by respiratory viruses. The semi-synthetic polysaccharide, Pentosan polysulfate sodium (PPS), an inhibitor of NF-kB activation, was investigated for its systemic and local anti-inflammatory effects in a mouse model of influenza virus A/PR8/1934 (PR8 strain) mediated infection.MethodsImmunocompetent C57BL/6J mice were infected intranasally with a sublethal dose of PR8 and treated subcutaneously with 3 or 6 mg/kg PPS or vehicle. Disease was monitored and tissues were collected at the acute (8 days post-infection; dpi) or post-acute (21 dpi) phase of disease to assess the effect of PPS on PR8-induced pathology.ResultsIn the acute phase of PR8 infection, PPS treatment was associated with a reduction in weight loss and improvement in oxygen saturation when compared to vehicle-treated mice. Associated with these clinical improvements, PPS treatment showed a significant retention in the numbers of protective SiglecF+ resident alveolar macrophages, despite uneventful changes in pulmonary leukocyte infiltrates assessed by flow cytometry. PPS treatment in PR8- infected mice showed significant reductions systemically but not locally of the inflammatory molecules, IL-6, IFN-g, TNF-a, IL-12p70 and CCL2. In the post-acute phase of infection, PPS demonstrated a reduction in the pulmonary fibrotic biomarkers, sICAM-1 and complement factor C5b9.DiscussionThe systemic and local anti-inflammatory actions of PPS may regulate acute and post-acute pulmonary inflammation and tissue remodeling mediated by PR8 infection, which warrants further investigation. |
| first_indexed | 2024-04-10T16:23:11Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-10T16:23:11Z |
| publishDate | 2023-02-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-16c400970330433ab50c1eca97d5d99d2023-02-09T10:10:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-02-011410.3389/fimmu.2023.10308791030879Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammationRavi Krishnan0Catherine J. M. Stapledon1Helen Mostafavi2Helen Mostafavi3Helen Mostafavi4Joseph R. Freitas5Joseph R. Freitas6Joseph R. Freitas7Xiang Liu8Xiang Liu9Xiang Liu10Suresh Mahalingam11Suresh Mahalingam12Suresh Mahalingam13Ali Zaid14Ali Zaid15Ali Zaid16Research and Development, Paradigm Biopharmaceuticals Ltd., Melbourne, VIC, AustraliaResearch and Development, Paradigm Biopharmaceuticals Ltd., Melbourne, VIC, AustraliaEmerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, AustraliaSchool of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD, AustraliaGlobal Virus Network (GVN) Center for Excellence in Arboviruses, Griffith University, Gold Coast, QLD, AustraliaEmerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, AustraliaSchool of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD, AustraliaGlobal Virus Network (GVN) Center for Excellence in Arboviruses, Griffith University, Gold Coast, QLD, AustraliaEmerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, AustraliaSchool of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD, AustraliaGlobal Virus Network (GVN) Center for Excellence in Arboviruses, Griffith University, Gold Coast, QLD, AustraliaEmerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, AustraliaSchool of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD, AustraliaGlobal Virus Network (GVN) Center for Excellence in Arboviruses, Griffith University, Gold Coast, QLD, AustraliaEmerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, AustraliaSchool of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD, AustraliaGlobal Virus Network (GVN) Center for Excellence in Arboviruses, Griffith University, Gold Coast, QLD, AustraliaIntroductionThere is an unmet medical need for effective anti-inflammatory agents for the treatment of acute and post-acute lung inflammation caused by respiratory viruses. The semi-synthetic polysaccharide, Pentosan polysulfate sodium (PPS), an inhibitor of NF-kB activation, was investigated for its systemic and local anti-inflammatory effects in a mouse model of influenza virus A/PR8/1934 (PR8 strain) mediated infection.MethodsImmunocompetent C57BL/6J mice were infected intranasally with a sublethal dose of PR8 and treated subcutaneously with 3 or 6 mg/kg PPS or vehicle. Disease was monitored and tissues were collected at the acute (8 days post-infection; dpi) or post-acute (21 dpi) phase of disease to assess the effect of PPS on PR8-induced pathology.ResultsIn the acute phase of PR8 infection, PPS treatment was associated with a reduction in weight loss and improvement in oxygen saturation when compared to vehicle-treated mice. Associated with these clinical improvements, PPS treatment showed a significant retention in the numbers of protective SiglecF+ resident alveolar macrophages, despite uneventful changes in pulmonary leukocyte infiltrates assessed by flow cytometry. PPS treatment in PR8- infected mice showed significant reductions systemically but not locally of the inflammatory molecules, IL-6, IFN-g, TNF-a, IL-12p70 and CCL2. In the post-acute phase of infection, PPS demonstrated a reduction in the pulmonary fibrotic biomarkers, sICAM-1 and complement factor C5b9.DiscussionThe systemic and local anti-inflammatory actions of PPS may regulate acute and post-acute pulmonary inflammation and tissue remodeling mediated by PR8 infection, which warrants further investigation.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1030879/fullinfluenza A virusPentosan polysulfate sodiumacute inflammationcytokines and chemokineslung consolidationlung fibrosis |
| spellingShingle | Ravi Krishnan Catherine J. M. Stapledon Helen Mostafavi Helen Mostafavi Helen Mostafavi Joseph R. Freitas Joseph R. Freitas Joseph R. Freitas Xiang Liu Xiang Liu Xiang Liu Suresh Mahalingam Suresh Mahalingam Suresh Mahalingam Ali Zaid Ali Zaid Ali Zaid Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation Frontiers in Immunology influenza A virus Pentosan polysulfate sodium acute inflammation cytokines and chemokines lung consolidation lung fibrosis |
| title | Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation |
| title_full | Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation |
| title_fullStr | Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation |
| title_full_unstemmed | Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation |
| title_short | Anti-inflammatory actions of Pentosan polysulfate sodium in a mouse model of influenza virus A/PR8/34-induced pulmonary inflammation |
| title_sort | anti inflammatory actions of pentosan polysulfate sodium in a mouse model of influenza virus a pr8 34 induced pulmonary inflammation |
| topic | influenza A virus Pentosan polysulfate sodium acute inflammation cytokines and chemokines lung consolidation lung fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1030879/full |
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