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

Background 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. Objectives To investigate whether IL-4 and IL-5 mRNA are expressed earlier during late nasal responses and if so, which cell(s) are responsible. Methods 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. Results 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. Go-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 less than or equal to5% 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. Conclusions Eosinophils represent an early source of IL-4 which may contribute to TH2-type responses during late nasal responses and ongoing allergic rhinitis.