A novel murine model of occupational rhinitis following inhalation of toluene diisocyanate.
Johnson-VJ; Yucesoy-B; Luster-MI
Toxicologist 2007 Mar; 96(1):281
Diisocyanates are low molecular weight chemicals that have been identified as the leading cause of occupational asthma. Epidemiological evidence suggests that diisocyanate- induced rhinitis is a comorbid and often preceding condition in patients with occupational asthma. Understanding the pathogenesis of occupational rhinitis and its biological and chronological relationship with asthma will be critical for disease prevention. In this regard, we have developed a murine model of toluene diisocyanate (TDI)-induced rhinitis. Female C57BL/6 mice were exposed to TDI vapor via inhalation for 4 hours/day for 12 days with or without a 2 week rest period and TDI challenge. The nasal mucosa was examined after each experimental stage for alterations in cytokine expression and pathology. Mice exposed to TDI vapor for 2 weeks showed elevated expression of IL-4, IL-5, IL-13, IL-10 and IFNgamma suggesting a mixed Th1/Th2 immune response. Expression of proinflammatory cytokines (TNFalpha and IL-1beta) and adhesion molecules (VCAM-1 and ICAM-1) was also upregulated. These cytokine changes corresponded to a marked influx of inflammatory cells into the nasal mucosa, eosinophils being the predominant cell type. Removal from exposure for 2 weeks resulted in a reduction in cytokine expression and pathology to control levels. Subsequent challenge with TDI vapor resulted in robust upregulation of the same cytokine genes as well as eosinophilic inflammation. The present model shows that TDI inhalation induces allergic rhinitis displaying many of the cardinal features of human disease. Future work will use this model to define the immune mechanisms and also examine the temporal/dose relationship between TDI-induced rhinitis and asthma.
Animal-studies; Physical-reactions; Mathematical-models; Statistical-analysis; Physical-reactions; Drug-receptor; Drug-interaction; Risk-analysis; Risk-factors; Dose-response; Epidemiology; Bronchial-asthma; Inhalation-studies; Allergic-reactions; Allergic-disorders; Allergens; Allergies; Chemical-analysis; Chemical-composition; Chemical-hypersensitivity; Chemical-reactions
The Toxicologist. Society of Toxicology 46th Annual Meeting and ToxExpo, March 25-29, 2007, Charlotte, North Carolina