Airway hyperreactivity modulated by immunotherapy with denatured ovalbumin in ovalbumin-sensitized guinea pigs

Denatured immunogenic peptides have recently been used successfully to treat autoimmune disease in mice. Their effect on airway response is unclear. In this study, we compared the effect of native ovalbumin (OVA) and denatured ovalbumin (DN-OVA) on airway spasm and hyperreactivity in guinea pigs. The effects of immunotherapy using DN-OVA were also investigated. Airway response to antigen was determined in conscious, nose-breathing guinea pigs. Results showed that animals could be sensitized by repeated exposure to OVA, but not DN-OVA. Following OVA exposure in OVA-sensitized guinea pigs, airway resistance was significantly increased in both early (30 min, 118.8% +/- 34.2%) and late (6 h, 91.1% +/- 30.1%) phases. Tidal volumes were reduced in both early (47.5% +/- 12.0%) and late (43.8% +/- 10.3%) phases. This dual-phase airway spasm could not be induced by DN-OVA. In addition, there was no change in pulmonary function noted after DN-OVA exposure in OVA-sensitized guinea pigs. OVA-induced airway response was modulated by immunotherapy with subcutaneous DN-OVA administration for 3 weeks. OVA-specific IgG was also increased after immunotherapy. However, there was no significant change in pulmonary function after oral administration of DN-OVA in OVA-sensitized guinea pigs. We conclude that OVA, but not DN-OVA, can successfully induce dual-phase airway spasm in guinea pigs. These reactions can be modulated by immunotherapy with subcutaneously administered DN-OVA.