Animal models for diisocyanate asthma: answers for lingering questions.
OBJECTIVE
Diisocyanates are the leading cause of occupational asthma, the most commonly reported lung disease associated with the workplace. Clinical studies have implicated the immune system in the pathogenesis of occupational asthma, but ethical and moral issues prevent mechanistic investigations in humans. For this reason, the development and characterization of animal models are germane to further understanding of diisocyanate occupational asthma and to identify avenues for therapeutic intervention. This review will highlight important features of existing experimental animal models with emphasis on new developments.


RESULTS
Experimental animal models of diisocyanate occupational asthma have demonstrated an immunological basis for the disease. Mice can be sensitized by dermal or respiratory exposure, suggesting that either exposure route may be important in the workplace. Recent findings show that sensitized mice develop airway hyperreactivity and inflammation, reflective of human disease. The transfer of lymphocytes or serum from sensitized mice can cause clinical disease in naive mice. Transgenic animals have identified a role for specific immunity, including the involvement of T-helper type 1/2 responses as well as CD4 and CD8 T cells in diisocyanate occupational asthma. Recent animal models have shown that sensitization can occur through subchronic inhalation of vapor-phase diisocyanate at levels as low as 20 ppb.


CONCLUSIONS
Recent progress using animal models has been instrumental in furthering current understanding of the involvement of the immune system in disease pathogenesis. The demonstration of diisocyanate occupational asthma in a murine model after sub-chronic inhalation exposure at relevant exposure levels should provide opportunities for more accurate risk assessment data.
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, West Virginia 26505, USA. vjohnson3@cdc.gov
Matheson
Joanna M
JM
Luster
Michael I
MI
D000395:Air Pollutants, Occupational / Q000009:adverse effects; D000485:Allergens / Q000009:adverse effects; D000818:Animals; D001249:Asthma / Q000139:chemically induced* / Q000503:physiopathology; D003485:Cyanates / Q000009:adverse effects*; D006801:Humans; D017953:Isocyanates / Q000009:adverse effects*; D009784:Occupational Diseases / Q000139:chemically induced / Q000503:physiopathology; D001559:Benzhydryl Compounds
D000395:Air Pollutants, Occupational; D000485:Allergens; D003485:Cyanates; D017953:Isocyanates; C015262:1,6-hexamethylene diisocyanate; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds