The authors tested a hypothesis that lung inflammation and airway hyperresponsiveness (AHR) induced following barn air exposure are dependent on Toll-like receptor 4 (TLR4) by exposing C3HeB/FeJ (intact TLR4, wild type [WT]) and C3H/HeJ (defective TLR4, mutant) mice either to the barn air (8 hours/day for 1, 5, or 20 days) or ambient air. Both strains of mice, compared to their respective controls, showed increased AHR following 5 exposures but dampened AHR after 20 exposures to show lack of effect of TLR4 on AHR. However, swine barn air induced lung inflammation with recruitment of inflammatory cells and cytokine expression was observed in WT but not in mutant mice. These data show different roles of TLR4 in lung inflammation and AHR in mice exposed to swine barn air.

No abstract

Modern swine barns house large number of pigs in confined buildings. The barn air contains microbes, dust, gases and endotoxin. Swine farmers experience loss of lung function and suffer from respiratory diseases. Exposure of naïve volunteers to swine barn air has shown to induce of lung inflammation and increased airway hyperresponsiveness (AHR) whose mechanisms remain unclear.We exposed rats to either swine barn or ambient air for eight hours per day for 1, 5 or 20 days. Following 20 day exposure and either 2 or 5 week recovery, rats were challenged either with saline or lipopolysaccharide. We measured AHR and lung inflammation. Exposure to barn induced AHR, mucus‐positive airway epithelial cells and lung inflammation while prolonged exposure dampened the AHR. Following barn exposures and recovery, rats showed lung inflammation with an increased intensity following lipopolysaccharide challenge.To clarify the role of Toll‐like receptor 4 (TLR4) in inducing lung inflammation and AHR, we exposed C3HeB/FeJ (intact TLR4, WT) and C3H/HeJ (defective TLR4, mutant) mice in a similar pattern. Both strains showed increased and dampened AHR following 5 and 20 exposures respectively while barn exposure induced lung inflammation in WT but not in mutant mice to show different roles of TLR4 in lung inflammation and AHR (CIHR's strategic training grant in PHARE and Lung Association of Saskatchewan).