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BMC Immunology
Published in: BMC Immunology 1/2020

Open Access 01-12-2020 | Glucocorticoid | Research article

Comparative efficacy of glucocorticoid receptor agonists on Th2 cell function and attenuation by progesterone

Authors: Alexander Luchak, Lauren A. Solomon, Tharsan Kanagalingam, Meerah Vijeyakumaran, Brian H. Rowe, Lisa Cameron

Published in: BMC Immunology | Issue 1/2020

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Abstract

Background

Corticosteroids (CS)s suppress cytokine production and induce apoptosis of inflammatory cells. Prednisone and dexamethasone are oral CSs prescribed for treating asthma exacerbations. While prednisone is more commonly prescribed, dexamethasone is long acting and a more potent glucocorticoid receptor (GR) agonist. It can be administered as a one or two dose regime, unlike the five to seven days required for prednisone, a feature that increases compliance. We compared the relative ability of these two oral CSs to suppress type 2 inflammation. Since progesterone has affinity for the GR and women are more likely to relapse following an asthma exacerbation, we assessed its influence on CS action.

Results

Dexamethasone suppressed the level of IL-5 and IL-13 mRNA within Th2 cells with ~ 10-fold higher potency than prednisolone (the active form of prednisone). Dexamethasone induced a higher proportion of apoptotic and dying cells than prednisolone, at all concentrations examined. Addition of progesterone reduced the capacity of both CS to drive cell death, though dexamethasone maintained significantly more killing activity. Progesterone blunted dexamethasone-induction of FKBP5 mRNA, indicating that the mechanism of action was by interference of the CS:GR complex.

Conclusions

Dexamethasone is both more potent and effective than prednisolone in suppressing type 2 cytokine levels and mediating apoptosis. Progesterone attenuated these anti-inflammatory effects, indicating its potential influence on CS responses in vivo. Collectively, our data suggest that when oral CS is required, dexamethasone may be better able to control type 2 inflammation, eliminate Th2 cells and ultimately lead to improved long-term outcomes. Further research in asthmatics is needed.
Appendix
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Metadata
Title
Comparative efficacy of glucocorticoid receptor agonists on Th2 cell function and attenuation by progesterone
Authors
Alexander Luchak
Lauren A. Solomon
Tharsan Kanagalingam
Meerah Vijeyakumaran
Brian H. Rowe
Lisa Cameron
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Immunology / Issue 1/2020
Electronic ISSN: 1471-2172
DOI
https://doi.org/10.1186/s12865-020-00383-8

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