title: Age Impacts Pulmonary Inflammation and Systemic Bone Response to Inhaled Organic Dust Exposure.
abstract: Agricultural workers have high rates of airway and skeletal health disease. Studies recently demonstrated that inhaled agricultural organic dust extract (ODE)-induced airway injury is associated with bone deterioration in an animal model. However, the effect of age in governing these responses to organic dusts is unclear, but might be important in future approaches. Young (7-9 wk) and older (12-14,o) male C57BL/6 mice received intranasal (i.n.) inhalation exposure to ODE from swine confinement facilities once or daily for 3 wk. Acute ODE-induced neutrophil influx and cytokine and chemokine (tumor necrosis factor [TNF]-α, interleukin [IL]-6, keratinocyte chemoattractant [CXCL1], macrophage inflammatory protein-2 [CXCL2]) airway production were reduced in older compared to young mice. Repetitive ODE treatment, however, increased lymphocyte recruitment and alveolar compartment histopathologic inflammatory changes in older mice. Whole lung cell infiltrate analysis revealed that young, but not older, mice repetitively treated with ODE demonstrated an elevated CD4:CD8 lymphocyte response. Acute inhalant ODE exposure resulted in a 4-fold and 1.5-fold rise in blood neutrophils in young and older mice, respectively. Serum IL-6 and CXCL1 levels were elevated in young and older mice i.n. exposed once to ODE, with increased CXCL1 levels in younger compared to older mice. Although older mice displayed reduced bone measurements compared to younger mice, younger rodents demonstrated ODE-induced decrease in bone mineral density, bone volume, and bone microarchitecture quality as determined by computed tomography (CT) analysis. Collectively, age impacts the airway injury and systemic inflammatory and bone loss response to inhalant ODE, suggesting an altered and enhanced immunologic response in younger as compared to older counterparts.
authors.affiliation: a Pulmonary, Critical Care, Sleep & Allergy Division , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Jill A
authors.initials: JA
authors.lastname: Poole
authors.affiliation: a Pulmonary, Critical Care, Sleep & Allergy Division , University of Nebraska Medical Center , Omaha , Nebraska , USA.|b Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha , Nebraska , USA.
authors.forename: Debra J
authors.initials: DJ
authors.lastname: Romberger
authors.affiliation: a Pulmonary, Critical Care, Sleep & Allergy Division , University of Nebraska Medical Center , Omaha , Nebraska , USA.|b Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha , Nebraska , USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Wyatt
authors.affiliation: a Pulmonary, Critical Care, Sleep & Allergy Division , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Staab
authors.affiliation: a Pulmonary, Critical Care, Sleep & Allergy Division , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Joel
authors.initials: J
authors.lastname: VanDeGraaff
authors.affiliation: b Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha , Nebraska , USA.|c Rheumatology Division, Department of Medicine , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Geoffrey M
authors.initials: GM
authors.lastname: Thiele
authors.affiliation: c Rheumatology Division, Department of Medicine , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Dusad
authors.affiliation: b Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha , Nebraska , USA.|c Rheumatology Division, Department of Medicine , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Lynell W
authors.initials: LW
authors.lastname: Klassen
authors.affiliation: b Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha , Nebraska , USA.|c Rheumatology Division, Department of Medicine , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Duryee
authors.affiliation: b Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha , Nebraska , USA.|c Rheumatology Division, Department of Medicine , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Ted R
authors.initials: TR
authors.lastname: Mikuls
authors.affiliation: d Department of Pathology , College of Medicine, University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: William W
authors.initials: WW
authors.lastname: West
authors.affiliation: e Pharmaceutical Sciences, College of Pharmacy , University of Nebraska Medical Center , Omaha , Nebraska , USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: a Pulmonary, Critical Care, Sleep & Allergy Division , University of Nebraska Medical Center , Omaha , Nebraska , USA.|b Veterans Affairs Nebraska-Western Iowa Health Care System , Omaha , Nebraska , USA.
authors.forename: Kristina L
authors.initials: KL
authors.lastname: Bailey
mesh_terms: D000281:Administration, Intranasal; D000367:Age Factors; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects*; D054360:Chemokine CXCL1 / Q000097:blood; D054426:Chemokine CXCL2 / Q000097:blood; D004391:Dust; D019570:Inhalation Exposure / Q000009:adverse effects*; D015850:Interleukin-6 / Q000097:blood; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011014:Pneumonia / Q000139:chemically induced*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D004391:Dust; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha