Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes

Antihistamines and glucocorticoids (GCs) are often used together in the clinic to treat several inflammation-related situations. Although there is no rationale for this association, clinical practice has assumed that, due to their concomitant anti-inflammatory effects, there should be an intrinsic b...

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Autores principales:	Carlos Daniel Zappia, Valeria Torralba-Agu, Emiliana Echeverria, Carlos P. Fitzsimons, Natalia Fernández, Federico Monczor
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	inflammation dexamethasone antihistamines glucocorticoids histamine Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/5b7ba3c60a49436aa5431328493637c9
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spelling	oai:doaj.org-article:5b7ba3c60a49436aa5431328493637c92021-11-25T17:10:32ZAntihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes10.3390/cells101130262073-4409https://doaj.org/article/5b7ba3c60a49436aa5431328493637c92021-11-01T00:00:00Zhttps://www.mdpi.com/2073-4409/10/11/3026https://doaj.org/toc/2073-4409Antihistamines and glucocorticoids (GCs) are often used together in the clinic to treat several inflammation-related situations. Although there is no rationale for this association, clinical practice has assumed that, due to their concomitant anti-inflammatory effects, there should be an intrinsic benefit to their co-administration. In this work, we evaluated the effects of the co-treatment of several antihistamines on dexamethasone-induced glucocorticoid receptor transcriptional activity on the expression of various inflammation-related genes in A549 and U937 cell lines. Our results show that all antihistamines potentiate GCs’ anti-inflammatory effects, presenting ligand-, cell- and gene-dependent effects. Given that treatment with GCs has strong adverse effects, particularly on bone metabolism, we also examined the impact of antihistamine co-treatment on the expression of bone metabolism markers. Using MC3T3-E1 pre-osteoblastic cells, we observed that, though the antihistamine azelastine reduces the expression of dexamethasone-induced bone loss molecular markers, it potentiates osteoblast apoptosis. Our results suggest that the synergistic effect could contribute to reducing GC clinical doses, ineffective by itself but effective in combination with an antihistamine. This could result in a therapeutic advantage, as the addition of an antihistamine may reinforce the wanted effects of GCs, while related adverse effects could be diminished or at least mitigated. By modulating the patterns of gene activation/repression mediated by GR, antihistamines could enhance only the desired effects of GCs, allowing their effective dose to be reduced. Further research is needed to correctly determine the clinical scope, benefits, and potential risks of this therapeutic strategy.Carlos Daniel ZappiaValeria Torralba-AguEmiliana EcheverriaCarlos P. FitzsimonsNatalia FernándezFederico MonczorMDPI AGarticleinflammationdexamethasoneantihistaminesglucocorticoidshistamineBiology (General)QH301-705.5ENCells, Vol 10, Iss 3026, p 3026 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	inflammation dexamethasone antihistamines glucocorticoids histamine Biology (General) QH301-705.5
spellingShingle	inflammation dexamethasone antihistamines glucocorticoids histamine Biology (General) QH301-705.5 Carlos Daniel Zappia Valeria Torralba-Agu Emiliana Echeverria Carlos P. Fitzsimons Natalia Fernández Federico Monczor Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes
description	Antihistamines and glucocorticoids (GCs) are often used together in the clinic to treat several inflammation-related situations. Although there is no rationale for this association, clinical practice has assumed that, due to their concomitant anti-inflammatory effects, there should be an intrinsic benefit to their co-administration. In this work, we evaluated the effects of the co-treatment of several antihistamines on dexamethasone-induced glucocorticoid receptor transcriptional activity on the expression of various inflammation-related genes in A549 and U937 cell lines. Our results show that all antihistamines potentiate GCs’ anti-inflammatory effects, presenting ligand-, cell- and gene-dependent effects. Given that treatment with GCs has strong adverse effects, particularly on bone metabolism, we also examined the impact of antihistamine co-treatment on the expression of bone metabolism markers. Using MC3T3-E1 pre-osteoblastic cells, we observed that, though the antihistamine azelastine reduces the expression of dexamethasone-induced bone loss molecular markers, it potentiates osteoblast apoptosis. Our results suggest that the synergistic effect could contribute to reducing GC clinical doses, ineffective by itself but effective in combination with an antihistamine. This could result in a therapeutic advantage, as the addition of an antihistamine may reinforce the wanted effects of GCs, while related adverse effects could be diminished or at least mitigated. By modulating the patterns of gene activation/repression mediated by GR, antihistamines could enhance only the desired effects of GCs, allowing their effective dose to be reduced. Further research is needed to correctly determine the clinical scope, benefits, and potential risks of this therapeutic strategy.
format	article
author	Carlos Daniel Zappia Valeria Torralba-Agu Emiliana Echeverria Carlos P. Fitzsimons Natalia Fernández Federico Monczor
author_facet	Carlos Daniel Zappia Valeria Torralba-Agu Emiliana Echeverria Carlos P. Fitzsimons Natalia Fernández Federico Monczor
author_sort	Carlos Daniel Zappia
title	Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes
title_short	Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes
title_full	Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes
title_fullStr	Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes
title_full_unstemmed	Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes
title_sort	antihistamines potentiate dexamethasone anti-inflammatory effects. impact on glucocorticoid receptor-mediated expression of inflammation-related genes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5b7ba3c60a49436aa5431328493637c9
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Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related Genes

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