Post-Endotoxin Exposure-Induced Lung Inflammation and Resolution Consequences Beneficially Impacted by Lung-Delivered IL-10 Therapy

Details

• Personal Author:
  Gaurav R ; Gleason A ; Nelson AJ ; Poole JA ; Romberger DJ ; Schwab A ; Wyatt TA
• Description:
  Although lung diseases typically result from long-term exposures, even a robust, one-time exposure can result in long-lasting consequences. Endotoxin is a ubiquitous environmental/occupational inflammatory agent often used to model airway inflammation. Using a murine model, the return to lung homeostasis following high dose inhalant lipopolysaccharide (LPS, 10-100 µg) exposure were delineated over 2 weeks. LPS-induced rapid weight loss, release of proinflammatory mediators, and inflammatory cell influx with prolonged persistence of activated macrophages CD11c+CD11b+ and recruited/transitioning CD11cintCD11b+ monocyte-macrophages out to 2 weeks. Next, lung-delivered recombinant (r) interleukin (IL)-10 was intratracheally administered for 3 doses initiated 5 h following LPS (10 µg) exposure for 2 days. IL-10 therapy reduced LPS-induced weight loss and increased blood glucose levels. Whereas there was no difference in LPS-induced bronchoalveolar lavage airway fluid cellular influx, total lung cell infiltrates were reduced (37%) with rIL-10 treatment. Post-LPS exposure treatment with rIL-10 strikingly reduced lavage fluid and lung homogenate levels of tumor necrosis factor-alpha (88% and 93% reduction, respectively), IL-6 (98% and 94% reduction), CXCL1 (66% and 75% reduction), and CXCL2 (47% and 67% reduction). LPS-induced recruited monocyte-macrophages (CD11cintCD11b+) were reduced (68%) with rIL-10. Correspondingly, LPS-induced lung tissue CCR2+ inflammatory monocyte-macrophage were reduced with rIL-10. There were also reductions in LPS-induced lung neutrophils, lymphocyte subpopulations, collagen content, and vimentin expression. These findings support the importance of studying resolution processes for the development of treatment after unintended environmental/occupational biohazard exposures. Short-term, lung-delivered rIL-10 favorably hastened inflammatory recovery processes following acute, high dose inhalant LPS exposure. [Description provided by NIOSH]
• Subjects:
  Endotoxins Immune System Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Exposure Assessment Immune Reaction Laboratory Animals Lung Disease Lung Tissue Medical Treatment Therapeutic Agents
• ISSN:
  2045-2322
• Document Type:
  Text
• Funding:
  Cooperative Agreement ; Grant
• Genre:
  Journal Article
• Place as Subject:
  Nebraska ; OSHA Region 7
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  12
• NIOSHTIC Number:
  nn:20066187
• Citation:
  Sci Rep 2022 Oct; 12:17338
• Contact Point Address:
  Jill A. Poole, Department of Internal Medicine, College of Medicine, University of Nebraska Medical Center, Omaha, NE, USA
• Email:
  japoole@unmc.edu
• Federal Fiscal Year:
  2023
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Scientific Reports
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:6cd46a41f49c9beb7649d3a34abdc7fa9c6348561da3d285844d9098e9bbb4d794acf61bcc894c7d467a299f3047249f62252b1f6a507079c317597a67f4b78c
• Download URL:
  https://stacks.cdc.gov/view/cdc/212684/cdc_212684_DS1.pdf
• File Type:
  [PDF - 1.17 MB ]