HDM induces direct airway inflammation in vivo: implications for future disease therapy?

¹ Respiratory Pharmacology, Pharmacology and Toxicology, Imperial College London, Faculty of Medicine, National Heart and Lung Institute, London SW7 2AZ, U.K.
² Respiratory CEDD. GlaxoSmithKline Research and Development, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, UK

^* To whom correspondence should be addressed. E-mail: m.belvisi{at}imperial.ac.uk.

	Abstract

House dust mite (HDM), the major source of allergen in house dust and strongly associated with the development of asthma, can evoke a direct, non-allergic, inflammatory reaction in vitro.

To determine whether this apparent non-allergic inflammatory response can be observed in a more complex in vivo setting.

Vehicle, Alum^TM or HDM (Der p 5μg, i.p. with Alum) sensitised Brown Norway rats were challenged intratracheally with vehicle (saline), HDM (Der p 10μg) or heat-inactivated HDM on day 21. Lung function changes and the associated inflammatory response were evaluated.

Tissue and BAL from Alum^TM sensitised Der p challenged animals exhibited strong eosinophilia and neutrophilia associated with an early release of pro-inflammatory cytokines (IL-13, IL-1, eotaxin, TARC). This response was not attenuated by removal of HDM-associated protease activity. Interestingly the vehicle sensitised group (no Alum^TM) lacked this inflammatory response.

HDM allergen evokes non-allergic airways inflammation with an inflammatory profile similar to that of the asthmatic airway. This response, independent of the protease activity of the HDM extract, appeared to be linked to prior administration of the adjuvant Alum^TM and the subsequent increase in total IgE. This finding could have important implications in the development of future asthma therapies.