Title: Immunomodulation in experimental feline asthma
Author(s): Norris, Carol Rose
Institution: University of California, Davis; 0029
Advisor: Adviser Laurel J. Gershwin
Source: DAI, 65, no. 06B (2004): p. 2841
Abstract: Cats naturally develop asthma that is remarkably close to the human disease; to study both, an experimental model of feline asthma was created using house dust mite and Bermuda grass allergen. Selection of clinically relevant allergens was performed by screening for allergen-specific IgE in pet cats with spontaneous asthma. Experimentally asthmatic cats developed clinical signs of asthma: serum allergen-specific IgE; increased serum and bronchoalveolar lavage fluid (BALF) allergen-specific IgG and IgA; airways hyperreactivity; airways eosinophilia; an early Th2 cytokine profile; and histologic evidence of airways remodeling.
This model was first used to evaluate novel therapeutics for pet cats with asthma. Results showed oral and inhaled corticosteroids significantly decreased airways eosinophilic inflammation, and although not statistically significant, the oral steroid and an anti-seritonergic drug reduced airway hyperresponsiveness in a subgroup of cats. Oral corticosteroids also decreased serum BGA-specific IgE. Unlike in humans asthmatics, a leukotriene receptor antagonist had no significant effect on inflammation or airways hyperresponsiveness.
The model was also used to evaluate the safety, efficacy, and immunologic mechanisms of rush immunotherapy (RIT). Rush immunotherapy dampens the immune response to allergen and involves administration of increasing doses of allergen given over a few days. Although not without risk, RIT significantly decreased BALF eosinophils compared with baseline, and altered cytokine profiles (decreased IL-4 and IL-5; increased Ifn-g and IL-10 in BALF). BGA-specific IgG significantly increased with RIT. The lymphocyte proliferative response to BGA also decreased at 6 months.
The last study examined CpG motifs (DNA sequences found in high frequency in bacteria that when recognized by vertebrate immune systems, allows mounting of a strongly protective Th1 bias). In our model, trials using different CpG motif sequences, routes of deliver), and doses per treatment were to performed to determine an optimal protocol. Results suggested that more than one protocol using CpG motifs had immunomodulatory effects in vivo. Although no treatment minimized clinical signs of airways hyperreactivity, most treatments dampened eosinophilic airways inflammation. Serum and BALF IgA levels decreased with some CpG treatments, as did BGA-specific lymphocyte proliferation. Future studies should focus improving the efficacy of CpG motifs, perhaps by concurrent administration of allergen.