title: The chemokine system as a therapeutic target in autoimmune thyroid diseases: a focus on the interferon-γ inducible chemokines and their receptor.
abstract: The recruitment, trafficking, and in situ maintenance of specific subsets of activated lymphocytes constitute crucial steps for the initiation and perpetuation of chronic autoimmune inflammation. The fact that, after IFN-γ stimulation, thyrocytes secrete CXCR3- binding chemokines, which in turn recruits Th1 lymphocytes expressing CXCR3 and secreting IFN-γ, strongly supports the concept that the interferon-γ inducible chemokines (CXCL9, CXCL10, and CXCL11) and their receptor CXCR3 play an important role in the initiation of autoimmune thyroid diseases (AITD). Thus, interfering with CXCR3 might result in the abrogation of the inflammatory process. The understanding of these pathogenetic mechanisms suggested novel therapeutic approaches, with a growing interest for finding a way to interrupt the interactions between chemokines and their receptors. In this review, we focus on the efforts performed in establishing new pharmacological compounds able to target the chemokine/chemokine receptors system as well as to prevent the secretion of CXCR3-binding chemokines, induced by pro-inflammatory cytokines. The crucial issue of selecting the relevant therapeutic targets in animal models of AITD was also discussed. Although some encouraging results have been reached, major hurdles were encountered on the way to success. As a result, we are still waiting for the first anti-chemokine anti-inflammatory drug. Given the importance of leukocytes recruitment to inflammatory sites, research will continue to address the issue of developing specific chemokine-receptor antagonists. We look forward to the development of these novel pharmacological compounds which will hopefully provide a more valid alternative to the currently used lifelong replacement therapies for AITD.
authors.affiliation: Unit of Internal Medicine and Endocrinology Fondazione Salvatore Maugeri IRCCS, Chair of Endocrinology, University of Pavia, 27100 Pavia, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Rotondi
authors.forename: Luca
authors.initials: L
authors.lastname: Chiovato
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D015195:Drug Design; D006111:Graves Disease / Q000188:drug therapy* / Q000276:immunology; D050031:Hashimoto Disease / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D019707:Receptors, Chemokine; D007371:Interferon-gamma