Journal
EUROPEAN RESPIRATORY JOURNAL
Volume 35, Issue 6, Pages 1377-1387Publisher
EUROPEAN RESPIRATORY SOC JOURNALS LTD
DOI: 10.1183/09031936.00022908
Keywords
Allergy; asthma; cytokines; house dust mite; inflammation; rodent
Categories
Funding
- GlaxoSmithKline
- BBSRC [BB/E52708X/1] Funding Source: UKRI
- MRC [G0800196] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E52708X/1] Funding Source: researchfish
- Medical Research Council [G0800196] Funding Source: researchfish
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House dust mite (HDM) is the major source of allergen in house dust and is strongly associated with the development of asthma. HDM can evoke a direct, nonallergic inflammatory reaction in vitro. We aimed to determine whether this apparent nonallergic, inflammatory response can be observed in a more complex in vivo setting. Vehicle, Alum (TM) or HDM (Dermatophagoides pteronyssinus 5 mu g, i.p. with Alum) sensitised Brown-Norway rats were challenged intratracheally with vehicle (saline), HDM (Der p 10 mu g) or heat-inactivated HDM on day 21. Lung function changes and the associated inflammatory response were evaluated. Tissue and bronchoalveolar lavage from Alum (TM) sensitised Der p challenged animals exhibited strong eosinophilia and neutrophilia associated with an early release of pro-inflammatory cytokines (interleukin-13 and 1 beta, eotaxin and thymus and activation-regulated chemokine). 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 nonallergic 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 immunoglobulin E. This finding could have important implications in the development of future asthma therapies.
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