title: Distinct immunohistochemical localization of IL-4 in human inflamed airway tissues. IL-4 is localized to eosinophils in vivo and is released by peripheral blood eosinophils.
abstract: Nasal polyposis and asthma are inflammatory conditions of the airways characterized by infiltration of activated inflammatory cells, particularly eosinophils. IL-4 is a multifunctional cytokine considered to play an important role in eosinophilic inflammation. We examined the cellular distribution of immunoreactive IL-4 in nasal polyps, as well as in the bronchial mucosa of both nonasthmatic control subjects (n = 6) and patients with well-characterized mild asthma (n = 6) subjected to a diluent or an allergen challenge. To determine eosinophilic contribution, tissue sections were counterstained with FITC after IL-4 immunostaining. No eosinophils were observed in the bronchial mucosa of nonasthmatic subjects. Nasal polyp tissues contained approximately 15 times more eosinophils per mm2 compared with bronchial tissues from asthmatics after a diluent challenge. Allergen challenge resulted in a marked increase in eosinophil density in bronchial tissues. A negligible number of cells immunostaining IL-4 was observed in bronchial tissues from nonasthmatic control subjects. The density of IL-4-positive cells in nasal polyp tissues was almost three times greater compared with asthmatics bronchial tissues after a diluent challenge. Approximately 90% of the IL-4-positive cells in bronchial tissues did not exhibit fluorescence after FITC counterstaining; in contrast, about 80% of the IL-4-positive cells in nasal polyp tissues did. We also show that peripheral blood eosinophils from allergic subjects express IL-4 mRNA by Northern blot analysis, particularly on stimulation with secretory IgA immune complexes. Finally, the supernatant of stimulated eosinophils contained approximately 50 pg/10(6) cells of IL-4 as determined by ELISA. These data demonstrate that eosinophils express the message and release IL-4 in vitro, and that these cells are the primary source of immunoreactive IL-4 in tissues undergoing chronic severe mucosal inflammation.
authors.affiliation: Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Nonaka
authors.forename: R
authors.initials: R
authors.lastname: Nonaka
authors.forename: K
authors.initials: K
authors.lastname: Woolley
authors.forename: E
authors.initials: E
authors.lastname: Adelroth
authors.forename: K
authors.initials: K
authors.lastname: Miura
authors.forename: Y
authors.initials: Y
authors.lastname: Okhawara
authors.forename: M
authors.initials: M
authors.lastname: Glibetic
authors.forename: K
authors.initials: K
authors.lastname: Nakano
authors.forename: P
authors.initials: P
authors.lastname: O'Byrne
authors.forename: J
authors.initials: J
authors.lastname: Dolovich
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood / Q000276:immunology*; D015152:Blotting, Northern; D004804:Eosinophils / Q000276:immunology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology; D015847:Interleukin-4 / Q000032:analysis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000097:blood / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D012137:Respiratory System / Q000276:immunology* / Q000473:pathology
chemical_list: D012333:RNA, Messenger; D015847:Interleukin-4