Interferon-gamma and Tumor Necrosis Factor-alpha Sustain Secretion of Specific CXC Chemokines in Human Thyrocytes: A First Step Toward a Differentiation between Autoimmune and Tumor-Related Inflammation?

different cell types during leukocyte infiltration, the histopathological hallmark of autoimmunity. Previous data demonstrate that thyrocytes secrete CXC chemokines, particularly CXCL8 and CXCL10. However, the physiopathological significance of such secretion and the effects of a combination of proinflammatory stimuli in terms of preferential CXCL8 and CXCL10 release remain unclear. Objective: The aim of this study was to investigate whether the secretion of chemokines by human thyrocytes is a generalized inflammatory response or whether it is dependent upon specific proinflammatory stimuli. Methods: CXCL8 and CXCL10 were measured in supernatants of human thyrocytes in primary cultures basally and after 24 h stimulation with interferon- (IFN) (1000 U/ml) and TNF (10 ng/ml), alone or in combination. Results: CXCL8 but not CXCL10 was detected in basal conditions. The two chemokines showed differences in their response to proinflammatory cytokines. Indeed, significant secretion of CXCL10 was induced by IFN (P 0.01) and not TNF, whereas CXCL8 was secreted in response to TNF (P 0.01) being inhibited by IFN (P 0.01). The combination of TNF plus IFN synergistically increased the IFN-induced CXCL10 secretion (P 0.01) and reversed the TNF- induced CXCL8 secretion (P 0.01). Conclusions: These results confirm that human thyrocytes secrete CXC chemokines and demonstrate that the secretion of CXCL8 and CXCL10 is sustained by specific proinflammatory cytokines or their combination, which ultimately determines the nature of the infiltrating lymphocytes inhumanthyroid diseases. These results indirectly support a major role for CXCL10 in thyroid autoimmunity whereas CXCL8 might be involved in tumor-related inflammation.