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  • Title: Expression of interleukin (IL)-4 and IL-5 proteins in asthma induced by toluene diisocyanate (TDI).
    Author: Maestrelli P, Occari P, Turato G, Papiris SA, Di Stefano A, Mapp CE, Milani GF, Fabbri LM, Saetta M.
    Journal: Clin Exp Allergy; 1997 Nov; 27(11):1292-8. PubMed ID: 9420133.
    Abstract:
    BACKGROUND: TDI-induced asthma exhibits clinical, functional and morphological similarities with allergen-induced asthma, suggesting that an immunological mechanism is involved in the sensitization to TDI. In vitro studies using the technique of cloning lymphocytes demonstrated that a great proportion of T-cell clones derived from bronchial mucosa of 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 bronchial mucosa to TDI in sensitized subjects, we performed a quantitative analysis of bronchial biopsies. METHODS: We obtained bronchial biopsies from six subjects with TDI asthma 48 h after an asthmatic reaction induced by TDI challenge (challenged group), in six subjects with TDI 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 determined by immunohistochemistry in the area 100 microm beneath the epithelial basement membrane. RESULTS: The characteristic increase of submucosal eosinophils, but not of mast cells and T-lymphocytes, was observed in the subjects with TDI-induced asthma when compared with controls. No differences were detected between the two groups of asthmatics. In the subjects with TDI-induced asthma, cell immunoreactivity for IL-5 was increased when compared with normal controls. There was no difference in the expression of IL-5 protein between challenged and chronic asthmatics. In contrast, the expression of IL-4 protein was increased only in the asthmatic subjects tested after recent exposure to TDI. CONCLUSIONS: We demonstrated that TDI asthma 48 h after specific bronchial challenge was associated with increased numbers of cells expressing IL-4 and IL-5, whereas chronic TDI asthma was associated with increased expression of IL-5, but not of IL-4. The results suggest that subjects who developed TDI asthma exhibit increased production of IL-5 even in the absence of a recent trigger by the exogenous sensitizer and that production of TH2-like cytokines in TDI-induced asthma may not always be co-ordinately regulated in vivo.
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