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

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.