title: Systemic IL-6 Effector Response in Mediating Systemic Bone Loss Following Inhalation of Organic Dust.
abstract: 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.
authors.affiliation: 1 Pulmonary, Critical Care, Sleep & Allergy Division, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Adam
authors.initials: A
authors.lastname: Wells
authors.affiliation: 1 Pulmonary, Critical Care, Sleep & Allergy Division, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.|2 Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha, Nebraska.
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Romberger
authors.affiliation: 2 Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha, Nebraska.|3 Rheumatology Division, Department of Medicine, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Thiele
authors.affiliation: 1 Pulmonary, Critical Care, Sleep & Allergy Division, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.|2 Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha, Nebraska.|4 Department of Environmental, Agricultural, and Occupational Health, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Wyatt
authors.affiliation: 1 Pulmonary, Critical Care, Sleep & Allergy Division, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Staab
authors.affiliation: 1 Pulmonary, Critical Care, Sleep & Allergy Division, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.|2 Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha, Nebraska.
authors.forename: Art J
authors.initials: AJ
authors.lastname: Heires
authors.affiliation: 2 Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha, Nebraska.|3 Rheumatology Division, Department of Medicine, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Lynell W
authors.initials: LW
authors.lastname: Klassen
authors.affiliation: 2 Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha, Nebraska.|3 Rheumatology Division, Department of Medicine, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Duryee
authors.affiliation: 2 Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha, Nebraska.|3 Rheumatology Division, Department of Medicine, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Ted R
authors.initials: TR
authors.lastname: Mikuls
authors.affiliation: 3 Rheumatology Division, Department of Medicine, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Anand
authors.initials: A
authors.lastname: Dusad
authors.affiliation: 5 Department of Pathology and Microbiology, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: William W
authors.initials: WW
authors.lastname: West
authors.affiliation: 6 Department of Pharmaceutical Sciences, College of Pharmacy, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: 1 Pulmonary, Critical Care, Sleep & Allergy Division, University of Nebraska Medical Center , The Nebraska Medical Center, Omaha, Nebraska.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Poole
mesh_terms: D000818:Animals; D015415:Biomarkers; D001854:Bone Marrow Cells / Q000378:metabolism; D001862:Bone Resorption / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004391:Dust; D018836:Inflammation Mediators / Q000378:metabolism; D019570:Inhalation Exposure / Q000009:adverse effects*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010010:Osteoclasts / Q000378:metabolism; D015398:Signal Transduction; D055114:X-Ray Microtomography
chemical_list: D015415:Biomarkers; D016207:Cytokines; D004391:Dust; D018836:Inflammation Mediators; D015850:Interleukin-6
keywords: IL-6; airway; bone; inflammation; injury; lung; mouse; organic dust; osteoclast; precursor