Do corticosteroids induce apoptosis in nasal polyp inflammatory cells? In vivo and in vitro studies

Abstract

Objective/Hypothesis: Corticosteroids are an effective treatment for nasal polyposis. The exact mechanism of action is not certain. Recent research demonstrates that apoptosis (programmed cell death) in inflammatory cells is an important factor in the resolution of inflammation, and apoptosis is induced in eosinophils in cell culture with steroids. We hypothesized that inflammatory cell apoptosis is a key feature of regression of nasal polyps on exposure to steroids and examined this hypothesis in vivo and in vitro. Methods: A double-blind, placebo-controlled pilot study of fluticasone propionate aqueous nasal spray (FPANS) in nasal polyposis in humans in vivo was undertaken, and the effect of treatment on indices of cell death and proliferation measured. In addition, explants of nasal polyp tissue were maintained in vitro in short-term tissue culture with dexamethasone at increasing doses (0.1-50 μmol) over varying time intervals and then analyzed for similar indices of proliferation and cell death. Results: Apart from a marginal increase in apoptotic:mitotic ratio in epithelium, little difference between the effect of FPANS and placebo was demonstrated in vivo. However, in vitro, apoptotic index was significantly increased in the stromal layers in relation to time of incubation (P = .0169), and a significant dose-response relationship was demonstrated at 24 hours between stromal cell apoptosis and dexamethasone concentration (P = .001). Eosinophil apoptosis was confirmed by in situ end labeling and transmission electron microscopy. No steroid or time effect on epithelial cells was demonstrated in vitro. Conclusion: Corticosteroids induce apoptosis in inflammatory cells in human nasal polyps in vitro. This is not reflected by a similar response to FPANS at 14 days in vivo, but may still play a part in regression of polyps with other forms of administration or at other time points.