Gabriele Di Lorenzo, Maria Luisa Pacor, Maria Esposito Pellitteri, Sebastiano Gangemi, Patrizia Di Blasi, Giuseppina Candore, Alfredo Colombo, Domenico Lio, Calogero Caruso, "In vitro effects of fluticasone propionate on IL-13 production by mitogen-stimulated lymphocytes", Mediators of Inflammation, vol. 11, Article ID 219857, 4 pages, 2002. https://doi.org/10.1080/09622935020138226
In vitro effects of fluticasone propionate on IL-13 production by mitogen-stimulated lymphocytes
Background: Corticosteroid administration produces multiple immunomodulatory effects, including down-regulation of cytokine production by CD4 T lymphocytes. Fluticasone propionate (FP) (Glaxo Smith&Kline, Greenford, UK), a highly lipophilic topical corticosteroid, has been shown to be safe and effective in the treatment of asthma and of both seasonal and perennial rhinitis.Aims: To gain insight into the mechanisms of FP therapeutic effects, we evaluated interleukin (IL)-13 (a type 2 cytokine that seemingly plays a pivotal role in allergic mechanisms) production by mitogen-stimulated peripheral blood mononuclear cells (MNC) in vitro, treated or not with FP.Methods: MNC from 10 healthy subjects and 10 asthmatic atopic patients with Parietaria allergy were stimulated v/v with phytohaemagglutinin (PHA) (50 γ/ml) or with complete medium alone as a control. Culture supernatants, in vitro treated or not with 10-7 or 10-8 M FP, were collected after 48 or 72 h incubation. IL-13 production was assessed by enzyme-linked immunosorbent assay. In random selected samples, after 4 or 24 h of cell cultures, RNA was extracted and IL-4 and IL-5 reverse transcriptase-polymerase chain reaction (RT-PCR) products analyzed.Results: At 48 h, there were no differences in IL-13 concentration in PHA-stimulated cultures between healthy subjects and asthmatic patients (93.6 ± 18.9 versus 111.0 ± 25.1 pg/ml). At 72 h, similar results were obtained (63.9 ± 3.0 versus 73.3 ± 2.5 pg/ml, respectively). At this time, however, IL-13 concentrations were significantly decreased versus 48 h both in asthmatics () and in controls (). Treatment with 10-7 M FP significantly reduced IL-13 production in healthy subjects and asthmatic patients both at 48 h (93.6 ± 18.9 versus 50.50 ± 10.6 pg/ml, , and 111.0 ± 25.1 versus 59.3 ± 13.6 pg/ml, , respectively) and at 72 h (63.9 ± 9.6 versus 35.5 ± 4.4 pg/ml, , and 73.3 ± 8.0 versus 40.7 ± 4.5 pg/ml, , respectively). Similar results were obtained with 10-8 M FP at 48 and 72 h. Accordingly, evaluation of RT-PCR products from selected cell samples showed a FP dosage-dependent inhibition of IL-4 and IL-5 mRNA production both for healthy subjects and asthmatic patients.Conclusions: FP in vitro impairs IL-13 production by PHA-stimulated MNC from asthmatic and control subjects. This strengthens previous suggestions that IL-13 inhibition by steroids may, at least in part, account for their therapeutic effects.
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