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

Nasal polyposis and asthma are inflammatory conditions of the airways characterized by infiltration of activated inflammatory cells, particu larly eosinophils. IL-4 is a multifunctional cytokine considered to pl ay an important role in eosinophilic inflammation. We examined the cel lular 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 contribu tion, tissue sections were counterstained with FITC after IL-4 immunos taining. No eosinophils were observed in the bronchial mucosa of nonas thmatic subjects. Nasal polyp tissues contained approximately 15 times more eosinophils per mm(2) compared with bronchial tissues from asthm atics after a diluent challenge. Allergen challenge resulted in a mark ed increase in eosinophil density in bronchial tissues. A negligible n umber of cells immunostaining IL-4 was observed in bronchial tissues f rom nonasthmatic control subjects. The density of IL-4-positive cells in nasal polyp tissues was almost three times greater compared with as thmatics bronchial tissues after a diluent challenge. Approximately 90 % of the IL-4-positive cells in bronchial tissues did not exhibit fluo rescence after FITC counterstaining; in contrast, about 80% of the IL- 4-positive cells in nasal polyp tissues did. We also show that periphe ral blood eosinophils from allergic subjects express IL-4 mRNA by Nort hern blot analysis, particularly on stimulation with secretory IgA imm une complexes. Finally, the supernatant of stimulated eosinophils cont ained approximately 50 pg/10(6) cells of IL-4 as determined by ELISA. These data demonstrate that eosinophils express the message and releas e IL-4 in vitro, and that these cells are the primary source of immuno reactive IL-4 in tissues undergoing chronic severe mucosal inflammatio n.