IL-9 and c-Kit+ mast cells in allergic rhinitis during seasonal allergen exposure: Effect of immunotherapy
Received 3 December 2004; received in revised form 4 March 2005; accepted 9 March 2005. published online 16 May 2005.
Background
IL-9 is an important stimulus for tissue infiltration by mast cells, a feature requiring concomitant activation of c-Kit.
Objectives
We assessed IL-9 expression and c-Kit+ mast cells in the nasal mucosa of patients with allergic rhinitis during seasonal pollen exposure and observed the effects of allergen immunotherapy.
Methods
We studied 44 patients with seasonal rhinitis and asthma before and 2 years after a double-blind trial of grass pollen immunotherapy. Nasal mucosal IL-9+ cells and c-Kit+ mast cells were assessed by means of immunochemistry. Cell types expressing IL-9 protein were determined by means of dual immunofluorescence. IL-9 mRNA–positive cells were assessed by means of in situ hybridization, and their phenotype was determined by using sequential immunohistochemistry and in situ hybridization.
Results
Nasal mucosal c-Kit+ mast cells were increased during the pollen season (P=.0001). IL-9 mRNA–positive cells also tended to increase (P=.1) and correlated with nasal EG2+ eosinophils (r=0.47, P=.05) and IL-5 mRNA-positive cells (r=0.54, P=.02). The cell sources of IL-9 included T cells, eosinophils, neutrophils, and mast cells. When compared with placebo, successful pollen immunotherapy markedly inhibited seasonal increases in nasal mucosal c-Kit+ mast cells (P=.001) and the seasonal expression of IL-9 mRNA–positive cells (P=.06). Immunotherapy also inhibited IL-9 protein expression from nonendothelial cell sources (P=.0007).
Conclusion
IL-9 is upregulated in the nasal mucosa during the pollen season and correlates with tissue infiltration by eosinophils. Successful pollen immunotherapy is associated with inhibition of seasonal increases in both nasal c-Kit+ mast cells and eosinophils. This effect might be explained, at least in part, by the reduced local expression of IL-9.
From Upper Respiratory Medicine, Imperial College London at the National Heart and Lung Institute, London, United Kingdom
Reprint request: Stephen R. Durham, MD, FRCP, Upper Respiratory Medicine, Imperial College London, National Heart and Lung Institute, Dovehouse St, London SW3 6LY, United Kingdom.
CP was supported by a research fellowship from the European Respiratory Society (Grant LTRF2002-037). This work was supported by the National Asthma Campaign (UK), Medical Research Council (UK), and ALK Abello (Horsholm, Denmark).
Disclosure of potential conflict of interest: C. Pilette is supported by a European Respiratory Society (ERS) fellowship. S. Durham has consultant arrangements with and has received grants–research support from ALK-Abello and is on the speakers' bureau for ALK-Abello, GalxoSmithKline, Aventis, and UCB. All other authors—none disclosed.
∗ These authors contributed equally to the present study.
ABSTRACT