Inhalation of toluene diisocyanate vapor induces allergic rhinitis in mice.
Diisocyanates are the leading cause of occupational asthma, and epidemiological evidence suggests that occupational rhinitis is a comorbid and preceding condition in patients who develop asthma. The goal of the present studies was to develop and characterize a murine model of toluene diisocyanate (TDI)-induced rhinitis. Female C57BL/6 mice were exposed to workplace-relevant concentrations of TDI vapor via inhalation for 4 h/day for 12 days with or without a 2-wk rest period and TDI challenge. Mice exposed 12 consecutive weekdays to 50 parts per billion TDI vapor showed elevated total serum IgE and increased TDI-specific IgG titers. Breathing rates were decreased corresponding with increased inspiratory time. TDI exposure elevated IL-4, IL-5, IL-13, and IFN-gamma mRNA expression in the nasal mucosa, suggesting a mixed Th1/Th2 immune response. Expressions of mRNA for proinflammatory cytokines and adhesion molecules were also up-regulated. These cytokine changes corresponded with a marked influx of inflammatory cells into the nasal mucosa, eosinophils being the predominant cell type. Removal from exposure for 2 wk resulted in reduced Ab production, cytokine mRNA expression, and cellular inflammation. Subsequent challenge with 50 parts per billion TDI vapor resulted in robust up-regulation of Ab production, cytokine gene expression, as well as eosinophilic inflammation in the nasal mucosa. There were no associated changes in the lung. The present model shows that TDI inhalation induces immune-mediated allergic rhinitis, displaying the major features observed in human disease. Future studies will use this model to define disease mechanisms and examine the temporal/dose relationship between TDI-induced rhinitis and asthma.
Johnson
Victor J
VJ
Toxicology and Molecular Biology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505, USA. vjohnson3@cdc.gov
Yucesoy
Berran
B
Reynolds
Jeff S
JS
Fluharty
Kara
K
Wang
Wei
W
Richardson
Diana
D
Luster
Michael I
MI
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D000918:Antibody Specificity; D016207:Cytokines / Q000096:biosynthesis; D004195:Disease Models, Animal; D005260:Female; D007073:Immunoglobulin E / Q000096:biosynthesis / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D009297:Nasal Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009784:Occupational Diseases / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D011897:Random Allocation; D012221:Rhinitis, Allergic, Perennial / Q000139:chemically induced* / Q000276:immunology* / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014051:Toluene 2,4-Diisocyanate / Q000008:administration & dosage* / Q000276:immunology*
D000336:Aerosols; D016207:Cytokines; D007074:Immunoglobulin G; D014051:Toluene 2,4-Diisocyanate; D007073:Immunoglobulin E