Fluticasone propionate reduces influenza infection of human macrophages

Steroids are a mainstay of treatment for chronic respiratory diseases, such as asthma and COPD. Intriguingly, data emerging from the 2009 flu pandemic suggests that corticosteroid may have explained the association of asthma with less severe outcomes in patients hospitalised with influenza1. Since macrophages are a major target of influenza infection, the aim of the present study was to analyse the effect of corticosteroids on macrophage infection by influenza.Human monocyte-derived macrophages (MDM) were exposed to H3N2 X31 influenza virus or UV-irradiated virus (UVX31) for 24 h in the presence or absence of 10–7 M fluticasone propionate (FP).No infection of lung macrophages or MDM was seen upon exposure to UVX31 but incubation with X31 resulted in a mean(SE) infection rate of 41(8)% as measured by flow cytometry of nucleoprotein (NP)-1+ cells. Concurrent treatment of infected MDM with FP reduced the number of NP-1+ events to 34(8)% (n=8, p=0.04). At the same time, FP caused a significant reduction in the macrophage activation marker, PD-L1 (4482(2007) specific mean fluorescence intensity (SMFI) vs 7180(3327) SMFI, n=5, p=0.03). Furthermore, when infected MDM treated with FP were incubated with autologous T cells, there was a significant reduction in CD8+ T cell IFN release as measured by ELISpot (mean 1582(409) spot forming colonies (SFC) vs 519(192) SFC, n=8, p=0.01).These data suggest that reductions in macrophage and T cell activation caused by steroids may be a re...
Source: European Respiratory Journal - Category: Respiratory Medicine Authors: Tags: 10.1 Respiratory Infections Source Type: research