In summary, we report a mouse model of sensitisation followed by long term allergen challenges leading to sustained allergic airway inflammation, goblet cell hyperplasia, peribronchial fibrosis, and impaired lung function.
Predominant IL-13 production after short term, but not after prolonged challenges has been seen in similar models of OVA sensitisation [5], [9].
Recently established murine models of allergen sensitisation followed by long term allergen challenges do not only lead to impaired lung function (similar to short term challenge models) but also to airway wall remodelling, a feature typical of chronic asthma.
In athletes who are atopic, have rhinitis, or have higher than normal levels of circulating immunoglobulin E (IgE), repeated injury repair of the airway epithelium is thought to create a model of 'passive sensitisation' of the bronchial smooth muscle and increase the risk for AHR.
Studies in both murine and human models proposed that the onset of sensitisation of the fetal immune system might be possible in utero [11] [13].
Th2 cytokines (IL-4, IL-5 and IL-13), which dominate many murine models of short term airway sensitisation, Th1cytokines (IFN-γ and IL-12), as well as IL-10, a cytokine associated with regulatory immune responses, were measured in BAL fluid by ELISA.
Interestingly, evidence of Th1 responses with IFN-γ production has also been found recently in a murine model of chronic airway sensitisation [9].
Using a murine model of systemic allergen sensitisation we compared the consequences of short and long term airway allergen challenges during eight subsequent weeks, monitoring lung function, airway inflammation, features of airway wall remodelling and immune responses.
The mechanism of sensitisation has been further investigated in the acquired cisplatin-resistant cell model and intrinsic cisplatin-resistant cell lines (Supplementary Figure 5).
Published data suggest that sensitisation to SM develops more frequently in patients who are already sensitised to allergens of HDM. 17 18 Sensitisation to SMs in the absence of sensitisation to Dermatophagoides spp has been proposed as a rare event.
