Expression of interleukin (IL)-4 and IL-5 proteins in asthma induced by toluene diisocyanate (TDI)

P. Maestrelli, P. Occari, G. Turato, S. A. Papiris, A. Di Stefano, C. E. Mapp, G. F. Milani, L. M. Fabbri, M. Saetta

Research output: Contribution to journalArticlepeer-review


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 100μm 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 TH2-1ike cytokines in TDI-induced asthma may not always be co-ordinately regulated in vivo.

Original languageEnglish
Pages (from-to)1292-1298
Number of pages7
JournalClinical and Experimental Allergy
Issue number11
Publication statusPublished - 1997


  • Cytokines
  • Immunohistology
  • Inflammation
  • Occupational asthma

ASJC Scopus subject areas

  • Immunology


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