P Maestrelli, A di Stefano, P Occari, G Turato, G Milani, F Pivirotto, CE Mapp, LM Fabbri and M Saetta
Institute of Occupational Medicine, University of Padova, Italy.

To determine the status of activation of lymphocytes and the role of cytokines on the inflammatory response of the bronchial mucosa in toluene diisocyanate (TDI) asthma, we performed a quantitative analysis of bronchial biopsies obtained from 15 subjects with TDI-induced asthma and seven normal control subjects. Markers of activation of lymphocytes (CD25 and Very Late activation Antigen-1, VLA-1) and expression of Tumor Necrosis Factor-alpha (TNF alpha) and interleukin-1 beta (IL-1 beta) were determined by immunohistology in the submucosa. Moreover, expression of adhesion molecules on endothelium of submucosal vessels was assessed. Asthmatic subjects had increased numbers of cells expressing CD25 and VLA-1 compared with the control group (p < 0.05). TNF alpha and IL-1 beta immunoreactivity was increased in asthmatics compared with control subjects (p < 0.01), whereas the expression of adhesion molecules, ICAM-1 and E-selectin, on vascular endothelium was not significantly different. No significant differences in the morphologic quantifications were observed between the asthmatics who had biopsies taken 2 d after TDI challenge (n = 7) and those with longer interval (21 +/- 8 d) between TDI challenge and biopsy (n = 8), suggesting that the increase in CD25, VLA-1, TNF alpha, and IL-1 beta was not due to an acute effect, but could be considered a part of the chronic inflammatory process of the airways. We conclude that the inflammatory response of the airways in TDI-induced asthma is characterized by persistent activation of lymphocytes and by chronic expression of proinflammatory cytokines.

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