Abstract
The effects of repeated exposure to a range of doses of swine barn dust (SBD) on airway hyperresponsiveness (AHR) and inflammation were evaluated using a mouse model system. A number of components, including endotoxin and a number of feed proteins, were identified in SBD, and mice were exposed 20 min/d for 14 d to a log dilution series of nebulized SBD suspensions. AHR to methacholine was measured using head-out whole-body plethysmography, and the methacholine concentration inducing a 20% decrease in pulmonary airflow (PC20 MCh) was calculated. At the end of the 14-d exposure period, bronchoalveolar lavage (BAL) fluids were recovered, cytokines (interleukin [IL]-1β, IL-6, keratinocyte-derived chemokine [KC], and tumor necrosis factor [TNF]) in BAL were measured by enzyme-linked immunosorbent assay (ELISA), and leukocytes in BAL were counted. The PC20 MCh was significantly lower in the group of mice that were exposed to the highest concentration of SBD than in controls or the group exposed to the lowest level of dust. Likewise, the group that was exposed to the highest level of SBD had significantly higher levels of IL-1β, KC, and TNF than controls and some other groups. There were substantially more lymphocytes and monocytes in the BAL from mice that were exposed to the higher levels of SBD for the 14-d period, but neutrophils were not a part of this response. The SBD exposures used in these experiments induced chronic inflammatory phenotype responses, as indicated by the predominance of lymphocytes and monocytes, but not neutrophils, in BAL and by inflammatory cytokines detected. The association between the PC20MCh and dose of SBD suggests that a threshold of susceptibility occurs after a relatively low, chronic exposure to SBD.
This work was supported by the Livestock Environmental Initiative of Agriculture and Agri-Food Canada (AAFC-LEI), the Canadian Network for Bacterial Pathogens of Swine (NSERC-CNBPS), the CIHR training program Public Health and Agricultural–Rural Ecosystem (PHARE), and a CIHR operating grant, via grants CPC-06, 225155, 53906. Agriculture and Agri-Food Canada (AAFC) is pleased to participate in the production of this publication. AAFC is committed to working with its industry partners to increase public awareness of the importance of the agri-food industry to Canada. Opinions expressed in this document are those of the authors and not necessarily those of the authors' departments. Published as number 375 in the Vaccine & Infectious Disease Organization journal series.