Abstract
Glucocorticoids (GC) are widely used in the treatment of SSc, although there is not much evidence to prove the benefits offered by these drugs in this disease. In this study, we evaluated the effects of a GC on cytokine production in peripheral blood mononuclear cells (PBMC) of SSc patients. The effect of dexamethasone (DEX) was evaluated in PBMC of 21 SSc patients and 10 healthy volunteers after stimulation of cells with anti-CD3 and anti-CD28. Cytokines IL-2, IL-4, IL-6, IL-10, IL-17A, IL-17F, IFN-γ, TNF, and IL-1β were quantified in the culture supernatant by CBA or ELISA. Of the patients evaluated in this study, 8 (38%) were taking corticosteroids, and esophageal dysfunction was more frequent in these patients when compared to those who did not take corticosteroids. DEX (1.000 nM) treatment in PBMC of SSc patients stimulated with anti-CD3 and anti-CD28 promoted a significant reduction in IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF, IL-1β (p < 0.001 for all), and IL-17F (p = 0.023) cytokines levels. We did not observe differences in response to in vitro treatment with DEX between groups of patients taking or not taking corticosteroids. In PBMC from healthy volunteers, we observed that DEX treatment significantly reduced IL-4, IFN-γ (p = 0.003 for both), IL-6, IL-10, IL-17A, and TNF (p = 0.002 for all) cytokines. These results show that DEX treatment in PBMC of SSc patients reduced the production of important cytokines involved in the pathogenesis of the disease, suggesting a possible mechanism of action of the CG in the treatment of SSc.
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Abbreviations
- CBA:
-
Cytometric bead array
- ELISA:
-
Enzyme-linked immunosorbent assay
- GC:
-
Glucocorticoids
- IL:
-
Interleukin
- IFN-γ:
-
Interferon gamma
- DEX:
-
Dexamethasone
- PBMC:
-
Peripheral blood mononuclear cells
- TFN:
-
Tumoral necrosis factor
- TGF-β:
-
Transforming growth factor-β
- SSc:
-
Systemic sclerosis
- dcSSc:
-
Diffuse cutaneous systemic sclerosis
- lcSSc:
-
Limited cutaneous systemic sclerosis
- α-SMA:
-
Alpha smooth muscle actin
- cDNA:
-
Complementary DNA
- SD:
-
Standard deviation
- IQR:
-
Interquartile range
- CT:
-
Computed tomography
- ANA:
-
Antinuclear antibodies
- ECM:
-
Extracellular matrix
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Acknowledgements
We would like to thank the team of reseachers from the Laboratório de Pesquisa Translacional of the Instituto de Medicina Integral Professor Fernando Figueira (IMIP), Leuridan C. Torres, Marina C. da Matta, and Kleber N. Jatahy for technical help.
Funding
This work was funded by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE) and Instituto Nacional de Ciência e Tecnologia para Inovação Farmacêutica (INCT-if).
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Chemical compound studied in this article: Dexamethasone (PubChem CID: 5743).
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de Almeida, A.R., Dantas, A.T., Pereira, M.C. et al. Dexamethasone inhibits cytokine production in PBMC from systemic sclerosis patients. Inflammopharmacol 27, 723–730 (2019). https://doi.org/10.1007/s10787-019-00600-w
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DOI: https://doi.org/10.1007/s10787-019-00600-w