EXPRESSION OF INTERLEUKIN (IL)-4 AND IL-5 PROTEINS IN ASTHMA INDUCED BY TOLUENE DIISOCYANATE (TDI)

Background TDI-induced asthma exhibits clinical, functional and morpho logical similarities with allergen-induced asthma, suggesting that an immunological mechanism is involved in the sensitization to TDI. In vi tro studies using the technique of cloning lymphocytes demonstrated th at a great proportion of T-cell clones derived from bronchial mucosa o f subjects with TDI-induced asthma produced IL-5 and interferon-gamma, but not IL-4, upon in vitro stimulation. Objectives To investigate in vivo the role of IL-4 and IL-5 on the inflammatory response of the br onchial mucosa to TDI in sensitized subjects, we performed a quantitat ive analysis of bronchial biopsies. Methods We obtained bronchial biop sies from six subjects with TDI asthma 48 h after an asthmatic reactio n induced by TDI challenge (challenged group), in six subjects with TD I asthma 1-4 weeks after the last exposure to TDI (chronic group), and in six non-asthmatic controls. The number of eosinophils, mast cells, T-lymphocytes, and IL-4 and IL-5 protein positive cells was determine d by immunohistochemistry in the area 100 mu m beneath the epithelial basement membrane. Results The characteristic increase of submucosal e osinophils, but not of mast cells and T-lymphocytes, was observed in t he subjects with TDI-induced asthma when compared with controls. No di fferences were detected between the two groups of asthmatics. In the s ubjects with TDI-induced asthma, cell immunoreactivity for IL-5 was in creased when compared with normal controls. There was no difference in the expression of IL-5 protein between challenged and chronic asthmat ics. In contrast, the expression of IL-4 protein was increased only in the asthmatic subjects tested after recent exposure to TDI. Conclusio ns We demonstrated that TDI asthma 48h after specific bronchial challe nge was associated with increased numbers of cells expressing IL-4 and IL-5, whereas chronic TDI asthma was associated with increased expres sion of IL-5, but not of IL-4. The results suggest that subjects who d eveloped TDI asthma exhibit increased production of IL-5 even in the a bsence of a recent trigger by the exogenous sensitizer and that produc tion of TH2-like cytokines in TDI-induced asthma may not always be co- ordinately regulated in vivo.