IMMUNOLOCALIZATION OF CYTOKINES IN THE NASAL-MUCOSA OF NORMAL AND PERENNIAL RHINITIC SUBJECTS - THE MAST-CELL AS A SOURCE OF IL-4, IL-5, AND IL-6 IN HUMAN ALLERGIC MUCOSAL INFLAMMATION

Allergic mucosal inflammation is characterized by the presence of cell infiltration, predominantly with IgE-sensitized mast cells and activated eosinophils, and appears to be regulated by the local production and release of several cytokines, particularly IL-4 and IL-5. Although attention has focused on the Th2 subpopulation of CD4+ T lymphocytes as an important source of these cytokines, human mast cells have been shown to both store and secrete IL-4 and TNF-alpha. To investigate the expression of cytokines relevant to allergic inflammation and to identify their cellular localization within the nasal mucosa, we have undertaken specific immunohistochemical staining of thin sections of inferior turbinate biopsies from patients with perennial allergic rhinitis and, for comparison, from nonatopic healthy volunteers. The cytokines investigated were IL-4, IL-5, IL-6, and IL-8. In both the normal and rhinitic biopsies numerous cells immunoreactive for IL-4, IL-5, and IL-6 were seen. Staining of adjacent 2-mum sections for CD3, mast cell tryptase, and eosinophil cationic protein revealed that 90% of the IL-4 immunoreactive cells were mast cells, with biopsies from rhinitic subjects containing significantly more IL-4+ cells than biopsies from normal controls (p = 0.02), especially when assessed with the anti-IL-4 mAb 3H4. Mast cells also accounted for >90% of IL-6 and >50% of IL-5 immunoreactive cells. IL-5 immunoreactivity was also localized to eosinophils, whereas IL-8 localized predominantly to the nasal epithelium in both groups. No cytokines were found in association with T lymphocytes. These findings indicate that the mast cell is an important source of preformed cytokines and as such may contribute to the chronicity of the mucosal inflammation that characterizes allergic rhinitis.