Changes in asthma-like responses after extended removal from exposure to trimellitic anhydride in the Brown Norway rat model.
Zhang-XD; Hubbs-AF; Siegel-PD
Clin Exp Allergy 2009 Nov; 39(11):1746-1753
Background: Organic acid anhydride-induced occupational asthma is considered to be IgE-mediated. Airway and skin exposure are the two main routes of sensitization in the work place. Recently we developed an allergic asthmatic Brown Norway rat model sensitized by dermal exposure to trimellitic anhydride (TMA) using an occlusion patch application. Objectives: The objectives of this study were (1) to develop a model of non-occluded dermal exposure leading to allergic sensitization and (2) to examine the effect of extended removal from exposure on persistence of both specific IgE and TMA aerosol-induced airway responses in this model. Methods: TMA powder (4 or 40 mg) was applied, unoccluded, to the skin of rats for 4 h, once/week for 4 weeks. Rats were given a 10-min aerosol challenge to 40 mg/m3 TMA 2 weeks after the last dermal exposure (day 35). Another group was challenged on day 35 and again 18-24 months later. Respiratory enhanced pause (Penh), pulmonary histopathology and inflammation and specific IgE titres were measured. Results: Rats produced dose-dependent specific IgE titres after exposure and developed early-phase (EAR) and late-phase airway responses (LAR) after airway challenge to TMA aerosol as well as airway eosinophilic inflammation. Specific airway responses were still manifested after a second TMA airway challenge given 18-24 months following the initial airway challenge. While persistent, airway inflammation, specific IgE and EAR were significantly attenuated following the second TMA challenge. LAR remained robust at 18-24 months and was not significantly different from the response on day 35. Conclusions: These results demonstrate the persistence of chemical sensitization and further suggest that IgE is not essential for LAR.
Bronchial-asthma; Respiratory-system-disorders; Pulmonary-system-disorders; Laboratory-animals; Animal-studies; Animals; Allergic-reactions; Allergies; Allergens; Airway-resistance
Paul D. Siegel, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505, USA
Clinical and Experimental Allergy