FP28-3 Role of corticosteroids and rapamycin on both Th1 and Th2 chemokines secretion, induced by cytokines, in orbital cells obtained from patients with Graves' ophthalmopathy

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP28-Thyroid Autoimmunity
Translational
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:55 AM
Room 103 (Moscone Center)

Poster Board SUN-437
Alessandro Antonelli*, Silvia Martina Ferrari, Poupak Fallahi, Ilaria Ruffilli, Andrea Di Domenicantonio, Stefano Sellari Franceschini and Ele Ferrannini
University of Pisa, Pisa, Italy
Introduction.Cytokines can influence the secretion of T helper (Th)1 and Th2 chemokines in fibroblasts, preadipocytes and myoblasts obtained from patients with Graves’ ophthalmopathy (GO). To our knowledge, no study has evaluated the effects of corticosteroids or rapamycin on the secretion of chemokines in GO orbital cells.

Methods.The effects of increasing concentrations of corticosteroids or rapamycin, on Th1 [chemokine (C-X-C motif) ligand 10 (CXCL10)] and Th2 [chemokine (C-C motif) ligand 2 (CCL2)] secretion in primary cultures of fibroblasts, preadipocytes and myoblasts  from the orbits of GO patients were tested.

Results.In primary cultures of fibroblasts, preadipocytes and myoblasts from GO patients, CXCL10 was undetectable in the supernatant, while low amounts of CCL2 were produced basally. Interferon(IFN)-gamma dose-dependently induced CXCL10 release, while had no effect on CCL2 secretion. Tumor necrosis factor(TNF)-alpha dose-dependently induced CCL2 release, but had no effect on CXCL10 secretion. However, the combination of TNF-alpha and IFN-gamma had a significant synergistic effect on both CXCL10 and CCL2 chemokines secretion. Increasing concentrations of corticosteroids or rapamycin (in a pharmacological range), added at the time of IFN-gamma and TNF-alpha stimulation, dose-dependently inhibited both CXCL10 and CCL2 release in GO fibroblasts, preadipocytes and myoblasts in primary cultures.

Conclusion.Corticosteroids or rapamycin, in a pharmacological range, play an inhibitory role both on Th1 (CXCL10) and Th2 (CCL2) chemokines, in GO orbital cells, suggesting the therapeutic effect of these drugs could be exerted, at least in part, through this mechanism.

Nothing to Disclose: AA, SMF, PF, IR, AD, SS, EF

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm