Serum IgE responses to Alternaria in Th1-biased Fisher-344 rats

Allergens containing proteases can induce Th2 responses in Th1-biased mice, including airway hyperresponsiveness, BAL eosinophilia, peribronchial inflammation, and airway goblet cell metaplasia. We hypothesized that exposing Th1-biased rats to protease-containing allergen (crude Alternaria) would result in a Th2-biased response (increase in crude Alternaria-specific IgE levels). Using Fisher-344 rats, we evaluated IgE responses to crude Alternaria exposure. Group 1 was sensitized subcutaneously to crude Alternaria in AlOH 3 at week 0 and exposed to nebulized crude Alternaria (150 mg protein) twice weekly for 5 weeks. Group 2 was sensitized subcutaneously to crude Alternaria in AlOH 3 at week 0 and exposed to intranasal crude Alternaria (0.6 mg protein) twice weekly for 5 weeks. Group 3 (not sensitized) was exposed to nebulized crude Alternaria (150 mg protein) twice weekly for 5 weeks. Group 4 (not sensitized) was exposed to nebulized saline twice weekly for 5 weeks. Blood samples were drawn weekly. Crude Alternaria-specific IgE levels were evaluated via ELISA. No statistically significant differences in crude Alternaria-specific IgE levels were demonstrated between groups (p>0.05). Protease content in the crude Alternaria extract (quantitated using a protease assay kit) was 130 ng/mg. Endotoxin level in the crude Alternaria extract (quantitated using an LAL test performed by Cambrex BioScience) was 21.5 EU/mg. We were unable to induce IgE responses to Alternaria in the Fisher-344 rat model. Neither the threshold dose of protease to induce Th2 responses or the threshold dose of endotoxin to induce Th1 responses in rodents are currently known.