Neutralisation of interleukin-13 in mice prevents airway pathology caused by chronic exposure to house dust mite.
BACKGROUND
Repeated exposure to inhaled allergen can cause airway inflammation, remodeling and dysfunction that manifests as the symptoms of allergic asthma. We have investigated the role of the cytokine interleukin-13 (IL-13) in the generation and persistence of airway cellular inflammation, bronchial remodeling and deterioration in airway function in a model of allergic asthma caused by chronic exposure to the aeroallergen House Dust Mite (HDM).


RESULTS
Mice were exposed to HDM via the intranasal route for 4 consecutive days per week for up to 8 consecutive weeks. Mice were treated either prophylactically or therapeutically with a potent neutralising anti-IL-13 monoclonal antibody (mAb) administered subcutaneously (s.c.). Airway cellular inflammation was assessed by flow cytometry, peribronchial collagen deposition by histocytochemistry and airway hyperreactivity (AHR) by invasive measurement of lung resistance (R(L)) and dynamic compliance (C(dyn)). Both prophylactic and therapeutic treatment with an anti-IL-13 mAb significantly inhibited (P<0.05) the generation and maintenance of chronic HDM-induced airway cellular inflammation, peribronchial collagen deposition, epithelial goblet cell upregulation. AHR to inhaled methacholine was reversed by prophylactic but not therapeutic treatment with anti-IL-13 mAb. Both prophylactic and therapeutic treatment with anti-IL-13 mAb significantly reversed (P<0.05) the increase in baseline R(L) and the decrease in baseline C(dyn) caused by chronic exposure to inhaled HDM.


CONCLUSIONS
These data demonstrate that in a model of allergic lung disease driven by chronic exposure to a clinically relevant aeroallergen, IL-13 plays a significant role in the generation and persistence of airway inflammation, remodeling and dysfunction.
Immunology Research, UCB, Slough, United Kingdom.
Kate L
KL
Tomlinson
Gareth C G
GC
Davies
Daniel J
DJ
Sutton
Roger T
RT
Palframan
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004781:Environmental Exposure; D005434:Flow Cytometry; D018793:Interleukin-13 / Q000276:immunology*; D016210:Methacholine Chloride / Q000008:administration & dosage; D051379:Mice; D008925:Mites; D009500:Neutralization Tests; D014132:Trachea / Q000473:pathology*; D015854:Up-Regulation
D018793:Interleukin-13; D016210:Methacholine Chloride