Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Glucocorticoids (GCs) have been used for more than 50 y as immunosuppressive drugs, yet their efficacy in macrophage-dominated disorders, such as chronic obstructive pulmonary disease, is debated. Little is known how long-term GC treatment affects macrophage responses in inflammatory conditions. In this study, we compared the transcriptome of human macrophages, matured in the presence or absence of fluticasone propionate (FP), and their ability to initiate or sustain classical activation, mimicked using acute LPS and chronic IFN-γ stimulation, respectively. We identified macrophage gene expression networks, modulated by FP long-term exposure, and specific patterns of IFN-γ- and LPS-induced genes that were resistant, inhibited, or exacerbated by FP. Results suggest that long-term treatment with GCs weakens adaptive immune signature components of IFN-γ and LPS gene profiles by downmodulating MHC class II and costimulatory molecules, but strengthens innate signature components by maintaining and increasing expression of chemokines involved in phagocyte attraction. In a mouse model of chronic obstructive pulmonary disease, GC treatment induced higher chemokine levels, and this correlated with enhanced recruitment of leukocytes. Thus, GCs do not generally suppress macrophage effector functions, but they cause a shift in the innate-adaptive balance of the immune response, with distinct changes in the chemokine-chemokine receptor network.

Original publication




Journal article


J immunol

Publication Date





1196 - 1208


Adaptive Immunity, Androstadienes, Animals, Budesonide, Cells, Cultured, Cytokines, Fluticasone, Gene Expression Regulation, Gene Regulatory Networks, Humans, Immunity, Innate, Interferon-gamma, Lipopolysaccharides, Lung, Macrophage Activation, Mice, Mice, Inbred C57BL, Pulmonary Disease, Chronic Obstructive, Receptors, Glucocorticoid, Specific Pathogen-Free Organisms, Th1 Cells, Tobacco Smoke Pollution, Toll-Like Receptor 4, Transcriptome