Vitamin D analogs decrease in vitro secretion of RANTES and enhance the effect of budesonide

ABSTRACTPurposeEosinophils appear to be central inflammatory cells in the pathogenesis of rhinosinusitis with nasal polyps (NP). One of the most predominantly recognized eosinophil chemoattractants is RANTES. The aim of this study was to assess the influence of vitamin D (VD) derivates on RANTES expression in the culture of nasal polyp fibroblasts.Material and methodsNP fibroblast cell cultures derived from 16 patients with NP were first stimulated with bacterial LPS and than incubated in increasing concentrations (from 10−7M to 10−4M) of calcitriol, tacalcitol or budesonide and in combination with one of VD derivate with budesonide in 1:1, 1:3 and 3:1 ratios. Quantitative analysis of RANTES level was conducted in culture supernatants using an ELISA method.ResultsThe highest calcitriol concentration (10−4M) as well as tacalcitol at 10−5M and 10−4M reduced RANTES production significantly compared to the control (201.1pg/ml, 338.7pg/ml, 211.3pg/ml v 571.78pg/ml; p<0.05). Budesonide and calcitriol administered in 1:3 ratio and budesonide and tacalcitol in 1:1 and 1:3 reduced RANTES concentration significantly better than each of the drug used in monotherapy (p<0.05). Budesonide and tacalcitol in 1:1 and 1:3 ratios suppressed RANTES production to the lowest level (171.8±97.6pg/ml and 178.7±105.22pg/ml, respectively).ConclusionActive VD compounds via downregulation of RANTES production exert a potential role as a complementary element in the therapy of chronic rhinosinusitis with NP. Compounds consisting of budesonide and VD derivate have an advantage over both drugs used in monotherapy.