House dust mite induces direct airway inflammation in vivo: implications for future disease therapy?
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 or HDM (Dermatophagoides pteronyssinus 5 microg, i.p. with Alum) sensitised Brown-Norway rats were challenged intratracheally with vehicle (saline), HDM (Der p 10 microg) or heat-inactivated HDM on day 21. Lung function changes and the associated inflammatory response were evaluated. Tissue and bronchoalveolar lavage from Alum sensitised Der p challenged animals exhibited strong eosinophilia and neutrophilia associated with an early release of pro-inflammatory cytokines (interleukin-13 and 1beta, 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) 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 and the subsequent increase in total immunoglobulin E. This finding could have important implications in the development of future asthma therapies.
Respiratory Pharmacology, Pharmacology and Toxicology, Faculty of Medicine, National Heart and Lung Institute, Imperial College London, Sir Alexander Fleming Building, Exhibition Road, London, SW7 2AZ, UK.
J
J
De Alba
K
K
Raemdonck
A
A
Dekkak
M
M
Collins
S
S
Wong
A T
AT
Nials
R G
RG
Knowles
M G
MG
Belvisi
M A
MA
Birrell
D000403:Airway Resistance / Q000276:immunology; D000534:Alum Compounds / Q000494:pharmacology; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000276:immunology*; D001249:Asthma / Q000276:immunology* / Q000628:therapy; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D016084:Bronchoconstriction / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000276:immunology; D008297:Male; D011014:Pneumonia / Q000276:immunology* / Q000628:therapy; D039981:Pyroglyphidae / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011914:Rats, Inbred BN; D013154:Spleen / Q000276:immunology
D000534:Alum Compounds; D039741:Antigens, Dermatophagoides; D018925:Chemokines; D016207:Cytokines; D012333:RNA, Messenger; D007073:Immunoglobulin E