ETA2022 Poster Presentations Graves’ Disease 1 (10 abstracts)
Corticosteroids and mycophenolic acid have a synergistic effect on chemokines secretion in orbital cells from patients with graves’ ophthalmopathy
Silvia Martina Ferrari 1 , Poupak Fallahi 2 , Francesca Ragusa 3 , Giusy Elia 3 , Sabrina Rosaria Paparo 3 , Armando Patrizio 4 , Eugenia Balestri 3 & Alessandro Antonelli 3
1University of Pisa, Department of Clinical and Experimental Medicine, Pisa, Italy; 2University of Pisa, Department of Translational Research of New Technologies in Medicine and Surgery, Pisa, Italy; 3University of Pisa, Department of Surgical, Medical and Molecular Pathology and Critical Area, Pisa, Italy; 4Azienda Ospedaliero-Universitaria Pisana, Department of Emergency Medicine, Pisa, Italy
Objective: An enhancement of the response rate has been recently showed in patients with Graves’ ophthalmopathy (GO) treated with corticosteroids and mycophenolic acid. In GO, retro-orbital cells showed a cytokine-induced secretion of Th1 and Th2 chemokines. Since no data are present in literature about the effect of corticosteroids and mycophenolic acid on the chemokines secretion in GO orbital cells, we aim to deepen out this topic.
Methods: We established primary cultures of myoblasts, preadipocytes and fibroblasts obtained from GO patients, and we tested increasing concentrations of mycophenolic acid or corticosteroids in order to study the effect on the secretion of either the Th1 (CXCL10) and Th2 (CCL2) chemokines.
Results: As regard the Th1 chemokines, we observed that CXCL10 was undetectable in the supernatants of the retro-orbital primary cultures cells, while IFNγ induced its release in a dose-dependent manner, and TNFα alone had no effect. By contrast, TNFα induced in a dose-dependent manner the release of the Th2 chemokine CCL2, whose amount is low in basal conditions, while IFNγ alone had no effect on the CCL2 secretion. The combination of TNFα and IFNγ had a significant synergistic effect on the CXCL10 and CCL2 secretion. Increasing concentrations of mycophenolic acid or corticosteroids (in a pharmacological range), were able to reduce the chemokines secretion in a dose-dependent manner, even in the presence of the IFNγ and TNFα stimulation. In addition, in presence of IFNγ and TNFα, the combination of corticosteroids and mycophenolic acid had a higher effect on the inhibition of the release of chemokines.
Conclusion: Our investigation showed the important role of mycophenolic acid and/or corticosteroids in the inhibition of the secretion of both Th1 (CXCL10) and Th2 (CCL2) chemokines. These findings suggest a possible therapeutic role of these drugs.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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