Cytokine expression during allergen-induced late nasal responses: IL-4 and IL-5 mRNA is expressed early (at 6 h) predominantly by eosinophils

Abstract

The production of TH2-type cytokines [interleukin-4 (IL-4) and IL-5] and tissue eosinophilia are characteristic features of allergic diseases. It was previously reported that at 24 h after allergen provocation, CD3+ T-lymphocytes were the principal cell source of IL-4 and IL-5 mRNA transcripts in both atopic asthma and rhinitis. To investigate whether IL-4 and IL-5 mRNA are expressed earlier during late nasal responses and if so, which cell(s) are responsible. Nasal biopsies were obtained at 6 h after nasal allergen challenge and following a control challenge with the allergen diluent. Sections were immunostained for T-lymphocytes (CD3+, CD4+) and eosinophils (EG2+). In situ hybridization was used to detect the number of cells expressing messenger RNA (mRNA) for IL-4 and IL-5. In patients with allergic rhinitis, eosinophils (EG2+ cells P = 0. 006) but not T- cells (CD3+ cells) increased in the nasal mucosa at 6 h after allergen challenge. The number of cells expressing IL-4 mRNA (P = 0.01) and IL-5 mRNA (P = 0.05) also increased at 6 h. Co-localization studies showed that 76% of IL-4 mRNA+ cells and 77% of IL-5 mRNA+ cells were eosinophils, whereas at this time point, T-cells and mast cells accounted for </=5% of mRNA expression; the identity of the remaining 20% of IL-4 and IL-5 mRNA+ cells was not determined. By use of immunohistology, cytokine protein expression at 6 h was confirmed for IL-4 but not for IL-5. No increases in T-cells, eosinophils or cytokine expression were detected in non-atopic subjects. Eosinophils represent an early source of IL-4 which may contribute to TH2-type responses during late nasal responses and ongoing allergic rhinitis.