In vitro Effect of Fluticasone Propionate on Interleukin 8 Production by Monocytes Obtained from Patients Affected by Moderate-Severe Allergic Asthma

BACKGROUND: Interleukin-8 (IL-8), a potent chemotactic and activating factor for neutrophils and eosinophils, may be a crucial factor in severe asthma. The aim of this study was to evaluate the effect of fluticasone propionate (FP), a corticosteroid with potent anti-inflammatory activity, on the in vitro release of IL-8 by monocytes obtained from asthmatic patients. METHODS: Monocytes from 15 non-atopic healthy donors and from 15 patients affected by moderate-severe allergic asthma were isolated and incubated (37 degrees C, 5% CO(2)) for 24 h with varying combinations of lipopolysaccharide (LPS) from Escherichia coli (1 microg/ml) and FP (100 nmol/l). IL-8 concentration in the culture supernatant was measured by an immuno-enzymatic method (ELISA). RESULTS: A highly significant inverse correlation between FEV1 (forced expiratory volume) values before withdrawal and in vitro IL-8 production by unstimulated monocytes from asthmatic patients was observed (Rho = -0.787; p = 0.0032). IL-8 production by either LPS-stimulated or unstimulated monocytes from asthmatic subjects was statistically increased compared to monocytes from healthy donors (p < 0.05). FP addition reduced IL-8 production by monocytes from asthmatic patients and also from healthy donors (p < 0.05). CONCLUSIONS: The partial IL-8 inhibition by FP could be closely related to the anti-inflammatory activity of this corticosteroid. Based on these results, we propose that the clinical improvement of asthma, observed following FP administration, may depend, at least in part, on the ability of this drug to modulate cytokine production by monocytes.