Lung-Delivered IL-10 Mitigates Lung Inflammation Induced by Repeated Endotoxin Exposures in Male Mice

Details

• Personal Author:
  Duryee MJ ; Gleason AM ; Mikuls TR ; Mosley DD ; Nelson AJ ; Poole JA ; Schanze OW ; Schwab AD ; Thiele GM ; Wyatt TA
• Description:
  Therapies capable of resolving inflammatory lung disease resulting from high-consequence occupational/environmental hazards are lacking. This study seeks to determine the therapeutic potential of direct lung-delivered interleukin (IL)-10 following repeated lipopolysaccharide exposures. C57BL/6 mice were intratracheally instilled with LPS (10 µg) and treated with IL-10 (1 µg) or vehicle control for 3 days. Lung cell infiltrates were enumerated by flow cytometry. Lung sections were stained for myeloperoxidase (MPO), CCR2, vimentin, and post-translational protein citrullination (CIT) and malondialdehyde-acetaldehyde (MAA) modifications. Lung function testing and longitudinal in vivo micro-CT imaging were performed. Whole lungs were profiled using bulk RNA sequencing. IL-10 treatment reduced LPS-induced weight loss, pentraxin-2, and IL-6 serum levels. LPS-induced lung proinflammatory and wound repair mediators (i.e., TNF-a, IL-6, CXCL1, CCL2, MMP-8, MMP-9, TIMP-1, fibronectin) were decreased with IL-10. IL-10 reduced LPS-induced influx of lung neutrophils, CD8+ T cells, NK cells, recruited monocyte-macrophages, monocytes, and tissue expression of CCR2+ monocytes-macrophages, MPO+ neutrophils, vimentin, CIT, and MAA. IL-10 reduced LPS-induced airway hyperresponsiveness and improved lung compliance. Micro-CT imaging confirmed the reduction in LPS-induced lung density by IL-10. Lung-delivered IL-10 therapy administered after daily repeated endotoxin exposures strikingly reduces lung inflammatory and wound repair processes to decrease lung pathologic changes and mitigate airway dysfunction. [Description provided by NIOSH]
• Subjects:
  Blood Endotoxins Environmental Exposure Immune System Lung Diseases Macrophages Occupational Exposure Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Author Keywords: Endotoxin Environmental Exposure Environmental Lung Disease Immune Reaction Inflammation Lung Disease Occupational Occupational Exposure
• ISSN:
  2051-817X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Kansas City Region [OSHA] ; Nebraska
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  13
• Issue:
  4
• NIOSHTIC Number:
  nn:20070523
• Citation:
  Physiol Rep 2025 Feb; 13(4):e70253
• Contact Point Address:
  Jill A. Poole, Division of Allergy & Immunology, University of Nebraska Medical Center, Omaha, Nebraska
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2025
• Performing Organization:
  University of Nebraska Medical Center
• Peer Reviewed:
  True
• Start Date:
  20210901
• Source Full Name:
  Physiological Reports
• End Date:
  20250831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:a2b21c51b9edbc3db40cfc3f4854b9e014e66316b8f701b79bf8a76efec23a6998175681b78dc8607c3067356624bb52782df1a0b7258fe7c63975c7e340898a
• Download URL:
  https://stacks.cdc.gov/view/cdc/208718/cdc_208718_DS1.pdf
• File Type:
  [PDF - 3.92 MB ]