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 activa ted eosinophils, and appears to be regulated by the local production a nd release of several cytokines, particularly IL-4 and IL-5. Although attention has focused on the Th2 subpopulation of CD4+ T lymphocytes a s an important source of these cytokines, human mast cells have been s hown to both store and secrete IL-4 and TNF-alpha. To investigate the expression of cytokines relevant to allergic inflammation and to ident ify their cellular localization within the nasal mucosa, we have under taken specific immunohistochemical staining of thin sections of inferi or turbinate biopsies from patients with perennial allergic rhinitis a nd, for comparison, from nonatopic healthy volunteers. The cytokines i nvestigated were IL-4, IL-5, IL-6, and IL-8. In both the normal and rh initic biopsies numerous cells immunoreactive for IL-4, IL-5, and IL-6 were seen. Staining of adjacent 2-mum sections for CD3, mast cell try ptase, and eosinophil cationic protein revealed that 90% of the IL-4 i mmunoreactive cells were mast cells, with biopsies from rhinitic subje cts containing significantly more IL-4+ cells than biopsies from norma l 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 immu noreactive cells. IL-5 immunoreactivity was also localized to eosinoph ils, whereas IL-8 localized predominantly to the nasal epithelium in b oth 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 th e mucosal inflammation that characterizes allergic rhinitis.