Granulocyte/Macrophage–Colony Stimulating Factor in Allergen–Induced Rhinitis: Cellular Localization, Relation to Tissue Eosinophilia and Influence of Topical Corticosteroid

Abstract

Background: Allergen–induced late nasal responses are associated with recruitment of T lymphocytes and eosinophils, and preferential messenger RNA (mRNA) expression of 'TH2–type' cytokines. We previously showed that topical steroid inhibited the late response and associated tissue eosinophilia. In this study we tested the hypothesis that granulocyte/macrophage–colony stimulating factor (GM–CSF) may contribute to late–responses and tissue eosinophilia and is inhibitable by topical corticosteroid. Methods: Nasal biopsies were taken before and 24 h after nasal allergen provocation following 6 weeks of treatment with either a nasal corticosteroid spray (fluticasone propionate) or a matched placebo nasal spray twice daily. Cryostat sections were processed by immunohistochemistry and in situ hybridization to assess cytokine mRNA expression for GM–CSF. Results: Increases in T lymphocytes and eosinophils were seen in the nasal mucosa after allergen challenge (p = 0.01) which were accompanied by a 5–fold increase in cells expressing mRNA for GM–CSF (p = 0.01). Double immunohistochemistry/in situ hybridization demonstrated that the majority of GM–CSF mRNA⁺ cells were co–localized to CD68+ (40%), or T cells (40%) with a lesser contribution from eosinophils (<20%). Topical steroid treatment was accompanied by a decrease in both the CD3+ and major basic protein (MBP+) cells expressing GM–CSF mRNA (p = 0.01) with a corresponding proportionate increase in the % of macrophages expressing GM–CSF. Conclusions: The results indicate that after allergen provocation, eosinophils are recruited to the nasal mucosa and that, at least in part, this may be due to GM–CSF. Topical nasal corticosteroid inhibits late responses and the associated eosinophilia, possibly indirectly by decreasing GM–CSF from T lymphocytes or reducing autocrine production of GM–CSF from eosinophils.