Characterisation of allergen induced airway hyperresponsiveness (AHR) in a murine model of allergic sensitisation

There is considerable variation in the protocols used to induce AHR in murine models of allergic sensitisation. With recent advances in the techniques used to measure lung physiology it is now possible to partition changes in lung resistance into airway & parenchymal responses. This study aimed to examine the changes in lung physiology in variations of a commonly used murine model of allergen induced airway inflammation.

Methods: Balb/c mice were systemically sensitised with ovalbumin (OVA) & challenged with 1, 3 or 6 OVA aerosols. AHR to methacholine (MCh) was assessed 24 & 48 h post-OVA challenge using a modification of the forcedoscillation technique to measure respiratory system impedance. Bronchoalveolar lavages (BAL) & blood were examined for inflammatory cell profiles, cytokines & IgE production.

Results: Mice challenged with 1 OVA aerosol had significantly increased airway resistance (Raw) (P = 0.043), tissue damping (G) (P = 0.002) & tissue elastance (H) (P = 0.001) responses to MCh challenge 24 h post-OVA compared to control mice, which had resolved by 48 h 3 or more OVA aerosols did not increase Raw but did cause a parenchymal response 24 h post-OVA (G, p = 0.025; H, p = 0.012) that was still evident after 48 h (G, p = 0.002; H, p = 0.004). Total cell counts (TCC) from BALs were significantly higher (P < 0.001) in mice challenged with 3 & 6 OVA aerosols compared to mice challenged with 1 OVA aerosol, which were higher (P < 0.001) than control TCC. There was no difference in TCC between mice 24 & 48 h post-OVA.

Conclusions: A single OVA aerosol induced transient airway & parenchymal responses to MCh while a higher number of OVA challenges caused a primarily parenchymal response that persisted beyond 48 h.