Monocyte chemotactic proteins in allergen-induced inflammation in the nasal mucosa: Effect of topical corticosteroids

BACKGROUND: Human allergen-induced rhinitis is associated with the recruitment and activation of inflammatory cells, particularly eosinophils and CD4(+) T cells, in the nasal mucosa. Chemokines are inflammatory mediators capable of attracting specific inflammatory cell populations. Monocyte chemotactic proteins (MCPs), a subfamily of CC chemokines, have been shown to induce chemotactic activity particularly in eosinophils, T cells, and monocytes under in vitro assay conditions. OBJECTIVE: To assess the contribution of MCPs in the recruitment of inflammatory cells in vivo, we investigated the allergen-induced late response in subjects with allergic rhinitis. METHODS: Patients were randomized to receive a 6-week treatment with either topical corticosteroid (n = 6) or a matched placebo (n = 6). Nasal inferior turbinate biopsy specimens were obtained from all subjects before and during allergen-induced late responses. By using immunocytochemistry, tissue sections were examined for the presence of MCP-1, MCP-3, and MCP-4 and for the phenotype of infiltrating cells within the nasal mucosa. In addition, double sequential immunocytochemistry was used to confirm the phenotype of MCP-immunoreactive positive cells. Furthermore, the effect of topical corticosteroids on the expression of MCPs and on the cellular infiltrate was also examined. RESULTS: MCP-1, MCP-3, and MCP-4 were expressed in all the baseline samples, with prominent staining observed within the nasal epithelium. Biopsy specimens taken after challenge exhibited significant upregulation in the expression of MCP-3 and MCP-4 (P <.001). On the other hand, this increase in response to allergen was reduced in patients pretreated with topical corticosteroids. Colocalization experiments revealed that the majority of MCP+ cells in the subepithelium were macrophages, followed by T cells and eosinophils. CONCLUSION: Our results demonstrate that allergen-induced rhinitis is associated with an increased expression of MCP-3 and MCP-4, which may be closely related to the influx of inflammatory cells and may thus contribute to the pathogenesis of allergic rhinitis.