Compared to healthy subjects, individuals with allergic airway disease (e.g.,
asthma,
allergic rhinitis) have enhanced inflammatory responses to inhaled
ozone. We created a rodent model of
ozone-enhanced allergic nasal responses in Brown Norway rats to test the
therapeutic effects of the dietary supplement
gamma-tocopherol (gammaT).
Ovalbumin (OVA)-sensitized rats were intranasally challenged with 0% or 0.5% OVA (in saline) on Days 1 and 2, and then exposed to 0 or 1 ppm
ozone (eight hours/day) on Days 4 and 5. Rats were also given 0 or 100 mg/kg gammaT (p.o., in
corn oil) on days 2 through 5, beginning twelve hours after the last OVA challenge. On Day 6, nasal tissues were collected for histological evaluation and morphometric analyses of intraepithelial mucosubstances (IM) and eosinophilic
inflammation. Nasal septal tissue was microdissected and analyzed by
reverse transcriptase polymerase chain reaction (RT-PCR) for
mucin glycoprotein 5AC (MUC5AC) expression levels. Histological analysis revealed mild to moderate eosinophil influx in the mucosa lining the nasal airways and maxillary sinus of OVA-challenged rats (eosinophilic
rhinosinusitis).
Ozone exposure of allergic rats further increased eosinophils in the maxillary sinus (400%), nasolacrimal duct (250%), and proximal midseptum (150%). Storage of intraepithelial mucosubstances (IM) was not significantly affected by OVA challenge in filtered air-exposed rats, but it was increased by
ozone in the septum (45%) and maxillary sinus (55%) of allergic compared to control rats. Treatment with gammaT attenuated the
ozone/ OVA-induced synergistic increases in IM and mucosal eosinophils in both nasal and paranasal airways.
gamma-Tocopherol also blocked OVA and
ozone-induced MUC5AC gene expression. Together, these data describe a unique model of
ozone enhancement of allergic
rhinosinusitis and the novel therapeutic efficacy of a common supplement, gammaT, to inhibit
ozone exacerbation of allergic airway responses.