title: Expression of interleukin (IL)-4 and IL-5 proteins in asthma induced by toluene diisocyanate (TDI).
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Institute of Occupational Medicine, University of Padova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Maestrelli
authors.forename: P
authors.initials: P
authors.lastname: Occari
authors.forename: G
authors.initials: G
authors.lastname: Turato
authors.forename: S A
authors.initials: SA
authors.lastname: Papiris
authors.forename: A
authors.initials: A
authors.lastname: Di Stefano
authors.forename: C E
authors.initials: CE
authors.lastname: Mapp
authors.forename: G F
authors.initials: GF
authors.lastname: Milani
authors.forename: L M
authors.initials: LM
authors.lastname: Fabbri
authors.forename: M
authors.initials: M
authors.lastname: Saetta
mesh_terms: D000328:Adult; D001249:Asthma / Q000139:chemically induced / Q000276:immunology*; D001706:Biopsy; D001980:Bronchi / Q000187:drug effects / Q000276:immunology*; D002908:Chronic Disease; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015847:Interleukin-4 / Q000096:biosynthesis*; D015848:Interleukin-5 / Q000096:biosynthesis*; D008297:Male; D008407:Mast Cells / Q000276:immunology; D008875:Middle Aged; D009092:Mucous Membrane / Q000276:immunology; D009784:Occupational Diseases / Q000139:chemically induced / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects*
chemical_list: D015848:Interleukin-5; D014051:Toluene 2,4-Diisocyanate; D015847:Interleukin-4