Animal models for diisocyanate asthma: answers for lingering questions.
Johnson-VJ; Matheson-JM; Luster-MI
Curr Opin Allergy Clin Immunol 2004 Apr; 4(2):105-110
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. 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. 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.
Animal-studies; Animals; Models; Bronchial-asthma; Toluenes; Lung-disease; Pulmonary-system-disorders; Respiratory-system-disorders; Immune-system-disorders
Victor J. Johnson, PhD, NIOSH, 1095 Willowdale Road, MS3014, Morgantown, WV 26505
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Current Opinion in Allergy and Clinical Immunology