Lung-Delivered IL-10 Therapy Elicits Beneficial Effects via Immune Modulation in Organic Dust Exposure-Induced Lung Inflammation

Details

• Personal Author:
  Gaurav R ; Gleason A ; Nelson AJ ; Poole JA ; Romberger DJ ; Schwab AD ; Wyatt TA
• Description:
  Efficacious therapeutic options capable of resolving inflammatory lung disease associated with environmental and occupational exposures are lacking. This study sought to determine the preclinical therapeutic potential of lung-delivered recombinant interleukin (IL)-10 therapy following acute organic dust exposure in mice. Here, C57BL/6J mice were intratracheally instilled with swine confinement organic dust extract (ODE) (12.5%, 25%, 50% concentrations) with IL-10 (1 µg) treatment or vehicle control intratracheally-administered three times: 5 hr post-exposure and then daily for 2 days. The results showed that IL-10 treatment reduced ODE (25%)-induced weight loss by 66% and 46% at Day 1 and Day 2 post-exposure, respectively. IL-10 treatment reduced ODE (25%, 50%)-induced lung levels of TNFa (-76%, -83% [reduction], respectively), neutrophil chemoattractant CXCL1 (-51%, -60%), and lavage fluid IL-6 (-84%, -89%). IL-10 treatment reduced ODE (25%, 50%)-induced lung neutrophils (-49%, -70%) and recruited CD11cintCD11b+ monocyte-macrophages (-49%, -70%). IL-10 therapy reduced ODE-associated expression of antigen presentation (MHC Class II, CD80, CD86) and inflammatory (Ly6C) markers and increased anti-inflammatory CD206 expression on CD11cintCD11b+ cells. ODE (12.5%, 25%)-induced lung pathology was also reduced with IL-10 therapy. In conclusion, the studies here showed that short-term, lung-delivered IL-10 treatment induced a beneficial response in reducing inflammatory consequences (that were also associated with striking reduction in recruited monocyte-macrophages) following acute complex organic dust exposure. [Description provided by NIOSH]
• Subjects:
  Agriculture Animals Dust Immune System Lung Diseases Occupational Health Respiratory Tract Diseases Safety
• Keywords:
  Animal Studies Author Keywords: Organic Dust Immune Reaction Immunology Inflammation Lung Disease Neutrophils Organic Dusts Therapeutic Agents Therapy
• ISSN:
  1547-691X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• 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:
  21
• Issue:
  1
• NIOSHTIC Number:
  nn:20069792
• Citation:
  J Immunotoxicol 2024 Apr; 21(1):2332172
• Contact Point Address:
  Aaron D. Schwab, Division of Allergy and Immunology, Nebraska Medical Center, Omaha, NE 68198, USA
• Email:
  aaron.schwab@unmc.edu
• Federal Fiscal Year:
  2024
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Nebraska Medical Center - Omaha
• Peer Reviewed:
  True
• Start Date:
  20110901
• Source Full Name:
  Journal of Immunotoxicology
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f256f8fbea66c46f3e150675243971d3cd0e10587aa09f194314918e3552e86598c47fbe74a40939aed9f3225d398dc13c0fc787ef1ba9421f122aae21c6b4da
• Download URL:
  https://stacks.cdc.gov/view/cdc/208148/cdc_208148_DS1.pdf
• File Type:
  [PDF - 2.98 MB ]