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https://hdl.handle.net/2440/7861
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Type: | Journal article |
Title: | Methyl-prednisolone up-regulates monocyte interleukin-10 production in stimulated whole blood |
Author: | Hodge, S. Hodge, G. Flower, R. Han, P. |
Citation: | Scandinavian Journal of Immunology, 1999; 49(5):548-553 |
Publisher: | WILEY |
Issue Date: | 1999 |
ISSN: | 0300-9475 1365-3083 |
Statement of Responsibility: | Hodge, S ; Hodge, G ; Flower, R ; Han, P |
Abstract: | Glucocorticosteroids (GCS) have been used successfully in the treatment of inflammatory conditions such as asthma and acute graft-vs-host disease, but their mode of action remains unclear. There have been numerous reports of the in-vitro suppression of cytokine production by GCS based on quantitation of cytokines by ELISA on bulk supernatants from isolated cell culture systems. We report the use of a whole-blood intracellular cytokine assay which is more representative of an in-vivo environment. We examined the effects of GCS, prednisolone and dexamethasone, on cytokine production by individual cells (monocytes, T lymphocytes and natural killer or NK cells) in heterogenous cell populations. Cells in whole blood were activated with various stimuli: phorbol ester and calcium ionophore for T cells, Escherichia coli lipopolysaccharide (LPS) for monocytes, and phytohaemagglutinin (PHA) plus interleukin (IL)-12 for NK cells. Brefeldin A was used as an intracellular transport inhibitor to enhance the detection of intracellular cytokine production. The effects of various concentrations (10-5, 10-7, 10-9 and 10-11 m) of GCS on cytokine production were studied using multiparameter flow cytometry. After surface staining with fluorescently-conjugated monoclonal antibodies (MoAbs) to identify cell type, cells were fixed and permeabilised. Intracellular cytokines interferon (IFN)-gamma, IL-10, IL-1alpha and beta, IL-2, tumour necrosis factor (TNF)-alpha, and IL-12 were stained with their respective conjugated MoAbs. The GCS both caused a dose-dependent modulation of cytokine production by T cells, monocytes and NK cells. After 4 h, a decrease in the MFI (amount of cytokine produced per cell) was noted for all cell types. After 24 h a decrease in both MFI and the percentage of cells producing cytokine was observed for all cell types. The exception was monocyte production of IL-10 which was enhanced at low concentrations of GCS (10-9 and 10-11 m). Our findings thus suggest that one anti-inflammatory mechanism of GCS action may be through inhibition of the release of pro-inflammatory cytokines IL-1alpha and beta, IL-2, IFN-gamma and TNF-alpha, and up-regulation of the anti-inflammatory cytokine IL-10. |
Keywords: | Monocytes Humans Methylprednisolone Anti-Inflammatory Agents Interleukin-10 Cytokines Glucocorticoids Up-Regulation Dose-Response Relationship, Drug Adult |
DOI: | 10.1046/j.1365-3083.1999.00538.x |
Published version: | http://dx.doi.org/10.1046/j.1365-3083.1999.00538.x |
Appears in Collections: | Aurora harvest Paediatrics publications |
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