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

Background: Human allergen-induced rhinitis is associated with the recruitm ent and activation of inflammatory cells, particularly eosinophils and CD4( +) T cells, in the nasal mucosa. Chemokines are inflammatory mediators capa ble of attracting specific inflammatory cell populations. Monocyte chemotac tic proteins (MCPs), a subfamily of CC chemokines, have been shown to induc e 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 inflamm atory 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 inferio r turbinate biopsy specimens were obtained from all subjects before and dur ing allergen-induced late responses. By using immunocytochemistry, tissue s ections were examined for the presence of MCP-1, MCP-3, and MCP-4 and for t he phenotype of infiltrating cells within the nasal mucosa In addition, dou ble sequential immunocytochemistry was used to confirm the phenotype of MCP -immunoreactive positive cells, Furthermore, the effect of topical corticos teroids on the expression of MCPs and on the cellular infiltrate was also e xamined. Results: MCP-1, MCP-3, and MCP-4 were expressed in all the baseline samples , with prominent staining observed within the nasal epitheliun. Biopsy spec imens taken after challenge exhibited significant upregulation in the expre ssion of MCP-3 and MCP-4 (P < .001). On the other hand, this increase in re sponse to allergen was reduced in patients pretreated with topical corticos teroids. Colocalization experiments revealed that the majority of MCP+ cell s in the subepithelium were macrophages, followed by T cells and eosinophil s. Conclusion: Our results demonstrate that allergen-induced rhinitis is assoc iated with an increased expression of MCP-3 and MCP-1, which may be closely related to the influx of inflammatory cells and may thus contribute to the pathogenesis of allergic rhinitis.