CYTOKINE MESSENGER-RNA EXPRESSION FOR IL-3, IL-4, IL-5, AND GRANULOCYTE/MACROPHAGE-COLONY-STIMULATING FACTOR IN THE NASAL-MUCOSA AFTER LOCAL ALLERGEN PROVOCATION - RELATIONSHIP TO TISSUE EOSINOPHILIA

Tissue eosinophilia is characteristic of human atopic allergic inflammation, although the mechanism is largely unknown. In this study we test the hypothesis that eosinophil infiltration during allergen-provoked rhinitis in hayfever sufferers may occur as a consequence of activation of a population of cells having a characteristic cytokine profile equivalent to the murine Th lymphocyte Th2 subset. Biopsies of the nasal inferior turbinate were obtained from 10 grass pollen-sensitive patients 24 h after local nasal provocation with allergen and after a control challenge with the allergen diluent. Biopsies were divided into two and subsequently processed for in situ hybridization using S-35-labeled RNA probes for selected cytokines and for immunohistology using an eosinophil granule mAb (EG2) which recognizes secreting eosinophils. At allergen-challenged sites compared with control sites there were significant increases in mRNA+ cells for IL-3 (p < 0.04), IL-4 (p = 0.01), IL-5 (p = 0.02) and granulocyte/macrophage-CSF (p = 0.03). In contrast, only occasional hybridization signals were observed for IL-2 and IFN-gamma at both allergen and control sites. After allergen there was an increase (p = 0.01) in EG2+ eosinophils and significant correlations were observed between EG2+ cells and mRNA expression for "Th2-type" cytokines, particularly IL-5 (r = 0.90, p < 0.0001). These results demonstrate that recruitment of eosinophils during human allergen-induced rhinitis is associated with cells expressing mRNA for IL-3, IL-4, IL-5, and granulocyte/macrophage-CSF.