Am. J. Respir. Crit. Care Med., Vol 154, No. 1, 07 1996, 201-208.
Inflammatory events in the blood and airways of guinea pigs immunized to toluene diisocyanate
CE Mapp, JR Lapa e Silva, RE Lucchini, P Chitano, V Rado, M Saetta, M Pretolani, MH Karol, P Maestrelli and LM Fabbri
Institute of Occupational Medicine, University of Padova, Italy.
Toluene diisocyanate (TDI)-induced asthma is a common cause of occupational
lung disease. We used a model to investigate the course of bronchopulmonary
inflammation following immunization with TDI. Guinea pigs were immunized by
weekly intradermal injections and challenged with TDI 7 d after the third
injection. The animals were killed at different times after challenge and
prepared for histologic examination of central and peripheral airways, for
immunohistochemical studies of T lymphocyte and eosinophil distribution,
and for hematologic and serologic investigations. Specific IgG1 against TDI
were present only in immunized animals. In immunized TDI-challenged animals
there was a significant increase in the number of metachromatic cells (at
24 h) and a late increase of eosinophils (at 48 h) in the peripheral blood.
Mast cells and eosinophils were also increased in the submucosa of central
airways of immunized TDI-challenged animals. A similar pattern was observed
in the animals' peripheral airways. Additionally, a significant increase of
T-lymphocytes and eosinophils was found in the lamina propria at 6 h after
exposure in immunized TDI-challenged animals as compared with control
animals. In these immunized animals, TDI challenge caused a significant
increase of eosinophils, T- lymphocytes, and CD4+ T cells. These findings
indicate that intradermal injections of TDI induced a specific antibody
response as well as an inflammatory process in both central and peripheral
airways. T cells, particularly CD4+ T cells and eosinophils, are the key
cells in the immunopathologic alterations induced by TDI in the guinea pig
lung.