Immunolocalization of cytokines to mast cells in normal and allergic conjunctiva

Background Recently, the potential role of mast cells in allergic reactions has been extended by the discovery that these cells synthesize, store and secrete multifunctional cytokines. Seasonal allergic conjunctivitis is characterized as an immediate hypersensitivity reaction, in which allergen binds to specitic IgE on mast cells, leading to release of preformed and newly synthesized inflammatory mediators. Objective In this study we aimed to localize the cytokines IL-4, IL-5, IL-6, IL-8 and TNFα to conjunctival mast cells and lo examine the relationship between mast cell-associated ctokines and allergic conjunctivitis. Methods Immunobistochemistry was perfonned on serial sections of conjunctival biopsies from patients with seasonal allergic conjunctivitis, in and out of tbe hay fever season, as well as from non-allergic volunteers. Results IL-4, IL-5, IL-6 and TNFα were localized to mast cells in normal and allergic conjunctiva. IL-8 was localized to mast cells in two patients with seasonal allergic conjunctivitis, one during and the other outside the pollen season. Using the monoclonal antibody 3H4, which identifies the secreted form of IL-4, biopsies frotn patients with active seasonal allergic conjunctivitis contained a significantly bigher proportion of mast cells positive for IL-4. than those from out-of-season patients (P= < 0.016). There was no difference between the two groups in the number of mast cells immunostained by the antibody 4D9 which identifies the stored form of IL-4. Conclusions These results suggest that conjunctival mast cells can store a range of multifunctional cytokines and release IL-4 during active disease, which may give them an important role in upregulating allergic inflamtnation in the conjunctiva.