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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MDPI AG
2021-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/10/11/3026 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T05:37:19Z |
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| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T05:37:19Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-5b7ba3c60a49436aa5431328493637c92023-11-22T22:50:13ZengMDPI AGCells2073-44092021-11-011011302610.3390/cells10113026Antihistamines Potentiate Dexamethasone Anti-Inflammatory Effects. Impact on Glucocorticoid Receptor-Mediated Expression of Inflammation-Related GenesCarlos Daniel Zappia0Valeria Torralba-Agu1Emiliana Echeverria2Carlos P. Fitzsimons3Natalia Fernández4Federico Monczor5Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, ArgentinaFacultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, ArgentinaFacultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, ArgentinaCenter for Neuroscience, Faculty of Science, Swammerdam Institute for Life Sciences, University of Amsterdam, 1098 XH Amsterdam, The NetherlandsFacultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, ArgentinaFacultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires 1113, ArgentinaAntihistamines 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.https://www.mdpi.com/2073-4409/10/11/3026inflammationdexamethasoneantihistaminesglucocorticoidshistamine |
| spellingShingle | 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 Cells inflammation dexamethasone antihistamines glucocorticoids histamine |
| title | 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_short | 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 |
| topic | inflammation dexamethasone antihistamines glucocorticoids histamine |
| url | https://www.mdpi.com/2073-4409/10/11/3026 |
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