Multiple exposures to swine barn air induce lung inflammation and airway hyper-responsiveness

Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, S7N 5B4, Canada.
Respiratory research (Impact Factor: 3.09). 06/2005; 6(1):50. DOI: 10.1186/1465-9921-6-50
Source: PubMed


Swine farmers repeatedly exposed to the barn air suffer from respiratory diseases. However the mechanisms of lung dysfunction following repeated exposures to the barn air are still largely unknown. Therefore, we tested a hypothesis in a rat model that multiple interrupted exposures to the barn air will cause chronic lung inflammation and decline in lung function.
Rats were exposed either to swine barn (8 hours/day for either one or five or 20 days) or ambient air. After the exposure periods, airway hyper-responsiveness (AHR) to methacholine (Mch) was measured and rats were euthanized to collect bronchoalveolar lavage fluid (BALF), blood and lung tissues. Barn air was sampled to determine endotoxin levels and microbial load.
The air in the barn used in this study had a very high concentration of endotoxin (15361.75 +/- 7712.16 EU/m3). Rats exposed to barn air for one and five days showed increase in AHR compared to the 20-day exposed and controls. Lungs from the exposed groups were inflamed as indicated by recruitment of neutrophils in all three exposed groups and eosinophils and an increase in numbers of airway epithelial goblet cells in 5- and 20-day exposure groups. Rats exposed to the barn air for one day or 20 days had more total leukocytes in the BALF and 20-day exposed rats had more airway epithelial goblet cells compared to the controls and those subjected to 1 and 5 exposures (P < 0.05). Bronchus-associated lymphoid tissue (BALT) in the lungs of rats exposed for 20 days contained germinal centers and mitotic cells suggesting activation. There were no differences in the airway smooth muscle cell volume or septal macrophage recruitment among the groups.
We conclude that multiple exposures to endotoxin-containing swine barn air induce AHR, increase in mucus-containing airway epithelial cells and lung inflammation. The data also show that prolonged multiple exposures may also induce adaptation in AHR response in the exposed subjects.

Download full-text


Available from: Chandrashekhar Charavaryamath, Sep 03, 2014
  • Source
    • "With increasing oxygen radicals, peroxidation of proteins, lipids, and nucleic acids a severe increase in responsiveness, secretion, and permeability of blood vessels occurs. In addition, free radicals activate inflammatory factors which result in exacerbation of allergic reactions (Murdoch and Lloyd, 2010 ▶; Charavaryamath, 2005 ▶). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective: Asthma is an airway complex disease defined by reversible airway narrowing and obstruction, chronic airway inflammation, airway hyperresponsiveness, and tissue remodeling. The purpose of this study was to determine the effect of Brassica napus L. (B. napus) on airway pathologic changes in a rat model of asthma. Materials and Methods: Twenty-four rats were divided into 4 groups: control, asthmatic, asthmatic treated with 0.5 mg/kg B. napus oil, and asthmatic treated with 0.75 mg/kg B. napus oil. To induce the experimental asthma, rats in groups 2, 3, and 4 received an i.p. injection of ovalbumin and aerosolized ovalbumin. Simultaneously, rats in groups 3 and 4 received B. napus oil daily by gavage. After 31 days, in all groups, thoracotomy was done and lung tissue samples were taken. For pathological evaluation, microscopic slides were prepared. The eosinophil numbers in the submucosal layer and thicknesses of smooth muscle layer of bronchioles were detected. Results: Eosinophil numbers in the submucosal layer, as well as smooth muscle layer thicknesses were significantly lower in the rat group treated with 0.75 mg/kg B. napus oil as compared with asthmatic group (p<0.01, p<0.05). Conclusion: B. napus could be useful as adjuvant therapy in rat model of asthma. This effect was probably related to its antioxidants components that reduce the levels of inflammatory mediators such as leukotrienes, IL-4, IL-5, and IL-13.
    Avicenna Journal of Phytomedicine 03/2013; 3(1):56-63.
  • Source
    • "Furthermore, changes in lung histology occur after MALP-2 aerosol administration, where the area of bronchus-associated lymphoid tissue is increased. The functional relevance of this finding remains to be investigated [28,29]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Toll-like receptors play an important role in innate and adaptive immunity and in balancing immune responses with tolerance. TLR2 is related to protection against allergies and allergic asthma by sensing pathogen associated patterns as lipoproteins and lipopeptides. A constant Th1 triggering is thought to prevent Th2 related disorders. TLR2 is expressed on a variety of cells, both structural as well as immune cells. Importantly, TLR2 is also expressed on dendritic cells, which are thought to be one of the key players of initiating and maintaining immune responses. Therefore, TLR2 on dendritic cells is a good target for modulating immunity either to Th1 or Th2 responses, or induction of tolerance. TLR2 agonists show high immunomodulatory and adjuvantic capacity. This makes TLR2 agonisation a promising approach for pharmaceutical intervention of allergic disorders.
    Journal of Occupational Medicine and Toxicology 03/2008; 3 Suppl 1(Suppl 1):S5. DOI:10.1186/1745-6673-3-S1-S5 · 1.62 Impact Factor
  • Source
    • "AHR was measured in awake control and exposed mice in response to increasing concentrations of methacholine (Mch) using head-out wholebody plethysmography as described [6] [17]. Briefly, air was supplied to the head and body compartments of the plethysmograph and changes in respiratory airflow were monitored using a flow sensor linked via a preamplifier and A/D board (Kent Scientific, Litchfield, CT) to a computer-driven realtime data acquisition/analysis system (DasyTec USA, Amherst, NH). "
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Experimental Lung Research 02/2008; 34(1):19-35. DOI:10.1080/01902140701807779 · 1.41 Impact Factor
Show more