Systemic IL-6 Effector Response in Mediating Systemic Bone Loss Following Inhalation of Organic Dust

Details

• Personal Author:
  Duryee MJ ; Dusad A ; Heires AJ ; Klassen LW ; Mikuls TR ; Poole JA ; Romberger DJ ; Staab E ; Thiele GM ; Wang D ; Wells A ; West WW ; Wyatt TA
• Description:
  Airway and skeletal diseases are prominent among agriculture workers. Repetitive inhalant exposures to agriculture organic dust extract (ODE) induces bone deterioration in mice; yet the mechanisms responsible for connecting the lung-bone inflammatory axis remain unclear. We hypothesized that the interleukin (IL)-6 effector response regulates bone deterioration following inhalant ODE exposures. Using an established intranasal inhalation exposure model, wild-type (WT) and IL-6 knockout (KO) mice were treated daily with ODE or saline for 3 weeks. ODE-induced airway neutrophil influx, cytokine/chemokine release, and lung pathology were not reduced in IL-6 KO animals compared to WT mice. Utilizing micro-computed tomography, analysis of tibia showed that loss of bone mineral density, volume, and deterioration of bone micro-architecture, and mechanical strength induced by inhalant ODE exposures in WT mice were absent in IL-6 KO animals. Compared to saline treatments, bone-resorbing osteoclasts and bone marrow osteoclast precursor populations were also increased in ODE-treated WT but not IL-6 KO mice. These results show that the systemic IL-6 effector pathway mediates bone deterioration induced by repetitive inhalant ODE exposures through an effect on osteoclasts, but a positive role for IL-6 in the airway was not demonstrated. IL-6 might be an important link in explaining the lung-bone inflammatory axis. [Description provided by NIOSH]
• Subjects:
  Agriculture Dust Immune System Laboratories Lung Lung Diseases Occupational Health Respiratory System Respiratory Tract Diseases Safety
• Keywords:
  Agricultural Workers Airway Author Keywords: IL-6 Bone Bone Disorders Cytokines Dust Exposure Etiology Exposure Assessment Immune Reaction Inflammation Inhalation Injury Laboratory Animals Lung Lung Disorders Molecular Signaling Mouse Organic Dust Organic Dusts Osteoclast Precursor

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• ISSN:
  1079-9907
• 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
• Pages in Document:
  9-19
• Volume:
  37
• Issue:
  1
• NIOSHTIC Number:
  nn:20052858
• Citation:
  J Interferon Cytokine Res 2017 Jan; 37(1):9-19
• Contact Point Address:
  Dr. Jill A. Poole, Pulmonary, Critical Care, Sleep & Allergy Division, Department of Medicine, University of Nebraska Medical Center, The Nebraska Medical Center, Omaha, NE 68198-5990
• Federal Fiscal Year:
  2017
• 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 Interferon & Cytokine Research
• End Date:
  20270831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:d8b018fe67933841b0380fd5e70bbba77ef6dab82b8ee802c14b506d430aaf5eddb6ea7dc53ade952af2785323d3dbc8efed8cceeec152073d403ad3b72a6fc1
• Download URL:
  https://stacks.cdc.gov/view/cdc/215773/cdc_215773_DS1.pdf
• File Type:
  [PDF - 771.61 KB ]