Cytokine profiles in airways of rats exposed to toluene diisocyanate

To investigate the status of cytokines in asthmatic airways induced by toluene diisocyanate (TDI), we established a Wistar rat model for asthma, and did a quantitative determination of cytokine production in asthmatic rats induced by TDI. Rats were sensitized with two courses of intranasal application of 10% TDI with each course for seven consecutive days, and then provoked with 5% TDI, and were followed by observation for airway symptoms. Bronchoalveolar lavage (BAL) was carried out, and total and differential leucocytes from BAL fluid were counted. Lungs were histopathologically examined for the status of inflammation in the airways. The selected cytokines, IL-2, IL-4, IL-6 and IFN-gamma productions, in BAL fluid in vivo and from BAL cells cultured in vitro were quantified with ELISA kits. The results showed that the rats with TDI sensitization exhibited asthmatic symptoms. TDI exposure resulted in an increase in the total number of cells, particularly eosinophils and neutrophils in BAL fluid. Histopathological examination showed a marked infiltration of central and peripheral airways with eosinophils in TDI-exposed rats. In TDI-sensitized rats, the productions of IL-4 and IL-6 in BAL fluid in vivo were markedly increased compared to that in control rats, but production of IL-2 and IFN-gamma was similar in the two groups. The cytokines from BAL cells cultured in vitro were released in a similar pattern as in vivo. These findings indicate that IL-4 and IL-6 are predominantly secreted in the airways and may play an important role in the pathogenesis of TDI-induced occupational allergic asthma.