Endocrine Abstracts

Introduction: No study has evaluated the effect of cytokines on the prototype beta chemokine (C-C motif) ligand (CCL)2 in Graves’ ophthalmopathy (GO), nor of peroxisome proliferator-activated receptor (PPAR)alpha activation on this chemokine secretion in fibroblasts or preadipocytes in GO.

Design and methods: We have tested the interferon (IFN)gamma and tumor necrosis factor (TNF)alpha effect on CCL2, and for comparison on the prototype alpha chemokine (C-X-C motif) ligand (CXCL)10, and the possible modulatory role of PPARalpha activation on these chemokines secretion in normal and GO fibroblasts or preadipocytes in primary cell cultures.

Results: The present study shows that IFNgamma alone, or in combination with TNFalpha was able to stimulate the secretion of CCL2 in primary orbital fibroblasts or preadipocytes from patients with GO, at levels similar to those observed in controls. IFNgamma and TNFalpha stimulated also CXCL10 chemokine secretion as expected. The presence of PPARalpha and -gamma in primary fibroblasts or preadipocytes from patients with GO has been confirmed. PPARalpha activators were able to inhibit the secretion of CXCL10 and CCL2, while PPARgamma activators were confirmed to be able to inhibit CXCL10, but had no effect on CCL2. PPARalpha activators were stronger inhibitors of chemokines secretion than PPARgamma agonists.

In conclusion, CCL2, and CXCL10, are modulated by IFNgamma and TNFalpha in GO. PPARalpha activators are able to inhibit the secretion of the main prototype alpha (CXCL10) and beta (CCL2) chemokines in GO fibroblasts or preadipocytes, suggesting that PPARalpha may be involved in the modulation of the immune response in GO.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector