title: Cytokines in the airway mucosa of subjects with asthma induced by toluene diisocyanate.
abstract: 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.
authors.affiliation: Institute of Occupational Medicine, University of Padova, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Maestrelli
authors.forename: A
authors.initials: A
authors.lastname: di Stefano
authors.forename: P
authors.initials: P
authors.lastname: Occari
authors.forename: G
authors.initials: G
authors.lastname: Turato
authors.forename: G
authors.initials: G
authors.lastname: Milani
authors.forename: F
authors.initials: F
authors.lastname: Pivirotto
authors.forename: C E
authors.initials: CE
authors.lastname: Mapp
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* / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism* / Q000473:pathology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis; D016207:Cytokines / Q000032:analysis*; D019040:E-Selectin; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007375:Interleukin-1 / Q000032:analysis; D007962:Leukocytes / Q000473:pathology; D008213:Lymphocyte Activation; D008297:Male; D008407:Mast Cells / Q000473:pathology; D009784:Occupational Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016029:Receptors, Very Late Antigen / Q000032:analysis; D014051:Toluene 2,4-Diisocyanate / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D019040:E-Selectin; D007375:Interleukin-1; D015375:Receptors, Interleukin-2; D016029:Receptors, Very Late Antigen; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D014051:Toluene 2,4-Diisocyanate