Abstract

Occupational asthma induced by toluene diisocyanate (TDI) shares several features with allergic asthma, but the mechanism of action of TDI is poorly understood. Ten sensitised subjects, previously shown to develop a dual or late asthmatic reaction after inhaling TDI were examined. In each subject, forced expiratory volume in one second (FEV1) was measured and venous blood was taken before, and 30 minutes and eight, 24, 48, and 72 hours after exposure to TDI (0.005-0.015 ppm for 10-30 minutes). Filtered air was used as a control. Differential leucocyte counts were determined and phenotypic analysis was performed by immunofluorescence on mononuclear cells using monoclonal antibodies (anti-CD3, anti-CD4, anti-CD8, and anti-HLA-DR). Five subjects developed a dual asthmatic reaction and five had a late reaction. Percentage of CD8 positive lymphocytes increased significantly eight hours after exposure to TDI (from 27 +/- 3 (SEM) % to 42.1 +/- 5%) in the subjects with an isolated late reaction. A delayed significant further increase in suppressor/cytotoxic T lymphocytes was seen in seven of the 10 subjects 48 hours after active exposure (from 27 +/- 2% to 42 +/- 4.8%), irrespective of the type of asthmatic reaction developed after exposure to TDI. Eosinophil percentage increased from 2.5% +/- 1.0 to 6.4% +/- 1.2 24 hours after exposure to TDI and the increase was sustained for up to 48 hours (4.7 +/- 1.1%). No significant variations of FEV1 or cell percentages were seen in the controls. In conclusion, the events triggered by exposure to TDI in sensitised subjects included changes in lung function and systemic effects which lasted longer than bonchoconstriction and concerned suppressor/cytotoxic lymphocytes and eosinophils. These results suggest that TDI induced late asthmatic reactions may be associated with an immunological response to TDI or to its products.