Cytokines as villains and potential therapeutic targets in thyroid-associated ophthalmopathy: from bench to bedside

References

• Ginsberg J, Shewring G, Smith BR. TSH receptor binding and thyroid stimulation by sera from patients with Graves’ disease. Clin Endocrinol (Oxf) 1983;19:305-11
   Google Scholar
• Feliciello A, Porcellini A, Ciullo I, et al. Expression of thyrotropin-receptor mRNA in healthy and Graves’ disease retro-orbital tissue. Lancet 1993;342:337-8
   PubMed Web of Science ®Google Scholar
• Stadlmayr W, Spitzweg C, Bichlmair AM, Heufelder AE. TSH receptor transcripts and TSH receptor-like immunoreactivity in orbital and pretibial fibroblasts of patients with Graves’ ophthalmopathy and pretibial myxedema. Thyroid 1997;7:3-12
   PubMedGoogle Scholar
• Antunes TT, Gagnon A, Bell A, Sorisky A. Thyroid-stimulating hormone stimulates interleukin-6 release from 3T3-L1 adipocytes through a cAMP-protein kinase A pathway. Obes Res 2005;13:2066-71
   Google Scholar
• Bell A, Gagnon A, Sorisky A. TSH stimulates IL-6 secretion from adipocytes in culture. Arterioscler Thromb Vasc Biol 2003;23:e65-6
   Google Scholar
• Douglas RS, Afifiyan NF, Hwang CJ, et al. Increased generation of fibrocytes in thyroid-associated ophthalmopathy. J Clin Endocrinol Metab 2010;95:430-8
   PubMed Web of Science ®Google Scholar
• Kumar S, Schiefer R, Coenen MJ, Bahn RS. A stimulatory thyrotropin receptor antibody (M22) and thyrotropin increase interleukin-6 expression and secretion in Graves’ orbital preadipocyte fibroblasts. Thyroid 2010;20:59-65
   PubMedGoogle Scholar
• Gillespie EF, Raychaudhuri N, Papageorgiou KI, et al. Interleukin-6 production in CD40-engaged fibrocytes in thyroid-associated ophthalmopathy: involvement of Akt and NF-κB. Invest Ophthalmol Vis Sci 2012;53:7746-53
   Google Scholar
• Raychaudhuri N, Fernando R, Smith TJ. Thyrotropin regulates il-6 expression in CD34(+) fibrocytes: clear delineation of its cAMP-independent actions. PLoS One 2013;8:e75100
   PubMed Web of Science ®Google Scholar
• Li B, Smith TJ. Regulation of IL-1 receptor antagonist by TSH in fibrocytes and orbital fibroblasts. J Clin Endocrinol Metab 2014;99(4):E625-33
   Google Scholar
• Baeten DL, Kuchroo VK. How Cytokine networks fuel inflammation: interleukin-17 and a tale of two autoimmune diseases. Nat Med 2013;19:824-5
   PubMed Web of Science ®Google Scholar
• Kotsovilis S, Andreakos E. Therapeutic Human Monoclonal Antibodies in inflammatory diseases. In: Michael Steinitz, editor. Human monoclonal antibodies: methods and protocols, methods in molecular biology. Volume 1060 Springer Science+Business Media; LLC; PA, USA: 2014;36-59
   Google Scholar
• Weetman AP, Cohen S, Gatter KC, et al. Immunohistochemical analysis of the retrobulbar tissues in Graves’ ophthalmopathy. Clin Exp Immunol 1989;75:222-7
   PubMed Web of Science ®Google Scholar
• Heufelder AE, Bahn RS. Detection and localization of cytokine immunoreactivity in retro-ocular connective tissue in Graves’ ophthalmopathy. Eur J Clin Invest 1993;23:10-17
   PubMed Web of Science ®Google Scholar
• Douglas RS, Gianoukakis AG, Goldberg RA, et al. Circulating mononuclear cells from euthyroid patients with thyroid-associated ophthalmopathy exhibit characteristic phenotypes. Clin Exp Immunol 2007;148:64-71
   Google Scholar
• Douglas RS, Gianoukakis AG, Kamat S, Smith TJ. Aberrant expression of the insulin-like growth factor-1 receptor by T cells from patients with Graves’ disease may carry functional consequences for disease pathogenesis. J Immunol 2007;178:3281-7
   PubMed Web of Science ®Google Scholar
• Douglas RS, Naik V, Hwang CJ, et al. B cells from patients with Graves’ disease aberrantly express the IGF-1 receptor: implications for disease pathogenesis. J Immunol 2008;181:5768-74
   PubMed Web of Science ®Google Scholar
• Feldon SE, Park DJ, O’Loughlin CW, et al. Autologous T-lymphocytes stimulate proliferation of orbital fibroblasts derived from patients with Graves’ ophthalmopathy. Invest Ophthalmol Vis Sci 2005;46:3913-21
   Google Scholar
• Bucala R, Spiegel LA, Chesney J, et al. Circulating fibrocytes define a new leukocyte subpopulation that mediates tissue repair. Mol Med 1994;1:71-81
   PubMed Web of Science ®Google Scholar
• Gillespie EF, Papageorgiou KI, Fernando R, et al. Increased expression of TSH receptor by fibrocytes in thyroid-associated ophthalmopathy leads to chemokine production. J Clin Endocrinol Metab 2012;97:E740-6
   Google Scholar
• Smith TJ, Padovani-Claudio DA, Lu Y, et al. Fibroblasts expressing the thyrotropin receptor overarch thyroid and orbit in Graves’ disease. J Clin Endocrinol Metab 2011;96:3827-37
   Google Scholar
• Fernando R, Atkins S, Raychaudhuri N, et al. Human fibrocytes coexpress thyroglobulin and thyrotropin receptor. Proc Natl Acad Sci U S A 2012;109:7427-32
   PubMed Web of Science ®Google Scholar
• Noden DM. Periocular mesenchyme: neural crest and mesodermal interactions. In: Jakobiec FA, editor. Ocular anatomy, embryology and teratology. Volume 97 Harper and Row; Philadelphia, PA, USA: 1982. p. 119
   Google Scholar
• Smith TJ, Ahmed A, Hogg MG, Higgins PJ. Interferon-gamma is an inducer of plasminogen activator inhibitor type 1 in human orbital fibroblasts. Am J Physiol 1992;263:C24-9
   Google Scholar
• Cao HJ, Hogg MG, Martino LJ, Smith TJ. Transforming growth factor-beta induces plasminogen activator inhibitor type-1 in cultured human orbital fibroblasts. Invest Ophthalmol Vis Sci 1995;36:1411-19
   PubMedGoogle Scholar
• Ishihara K, Hirano T. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine Growth Factor Rev 2002;13(4-5):357-68
   PubMed Web of Science ®Google Scholar
• Leech MD, Barr TA, Turner DG, et al. Cutting edge: IL-6-dependent autoimmune disease: dendritic cells as a sufficient, but transient, source. J Immunol 2013;190(3):881-5
   Google Scholar
• Kimura A, Kishimoto T. IL-6: regulator of Treg/Th17 balance. Eur J Immunol 2010;40(7):1830-5
   PubMed Web of Science ®Google Scholar
• Nepom GT, Ehlers M, Mandrup-Poulsen T. Anti-cytokine therapies in T1D: concepts and strategies. Clin Immunol 2013;149(3):279-85
   PubMed Web of Science ®Google Scholar
• Sempowski GD, Rozenblit J, Smith TJ, Phipps RP. Human orbital fibroblasts are activated through CD40 to induce proinflammatory cytokine production. Am J Physiol 1998;274:C707-14
   PubMed Web of Science ®Google Scholar
• Hwang CJ, Afifiyan N, Sand D, et al. Orbital fibroblasts from patients with thyroid-associated ophthalmopathy overexpress CD40: CD154 hyperinduces IL-6, IL-8, and MCP-1. Invest Ophthalmol Vis Sci 2009;50:2262-8
   PubMed Web of Science ®Google Scholar
• Raychaudhuri N, Douglas RS, Smith TJ. PGE2 induces IL-6 in orbital fibroblasts through EP2 receptors and increased gene promoter activity: implications to thyroid-associated ophthalmopathy. PLoS One 2010;5:e15296
   Google Scholar
• Celik I, Akalin S, Erbaş T. Serum levels of interleukin 6 and tumor necrosis factor-alpha in hyperthyroid patients before and after propylthiouracil treatment. Eur J Endocrinol 1995;132:668-72
   PubMed Web of Science ®Google Scholar
• Molnár I, Balázs C. High circulating IL-6 level in Graves’ ophthalmopathy. Autoimmunity 1997;25:91-6
   PubMed Web of Science ®Google Scholar
• Salvi M, Girasole G, Pedrazzoni M, et al. Increased serum concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor in patients with Graves’ disease. J Clin Endocrinol Metab 1996;81:2976-9
   PubMed Web of Science ®Google Scholar
• Salvi M, Pedrazzoni M, Girasole G, et al. Serum concentrations of proinflammatory cytokines in Graves’ disease: effect of treatment, thyroid function, ophthalmopathy and cigarette smoking. Eur J Endocrinol 2000;143:197-202
   PubMed Web of Science ®Google Scholar
• Pedro AB, Romaldini JH, Takei K. Changes of serum cytokines in hyperthyroid Graves’ disease patients at diagnosis and during methimazole treatment. Neuroimmunomodulation 2011;18:45-51
   PubMedGoogle Scholar
• Carswell EA, Old LJ, Kassel RL, et al. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A 1975;72:3666-70
   PubMed Web of Science ®Google Scholar
• Vendramini-Costa DB, Carvalho JE. Molecular link mechanisms between inflammation and cancer. Curr Pharm Des 2012;18(26):3831-52
   PubMed Web of Science ®Google Scholar
• Pichler R, Maschek W, Hatzl-Griesenhofer M, et al. Soluble tumour necrosis factor-alpha receptor I and interleukin-6 as markers of activity in thyrotoxic Graves’ disease. Horm Metab Res 2003;35:427-33
   PubMedGoogle Scholar
• Anvari M, Khalilzadeh O, Esteghamati A, et al. Graves’ disease and gene polymorphism of TNF-α, IL-2, IL-6, IL-12, and IFN-γ. Endocrine 2010;37:344-8
   PubMed Web of Science ®Google Scholar
• Kamizono S, Hiromatsu Y, Seki N, et al. A polymorphism of the 5’ flanking region of tumour necrosis factor alpha gene is associated with thyroid-associated ophthalmopathy in Japanese. Clin Endocrinol (Oxf) 2000;52:759-64
   Web of Science ®Google Scholar
• Zheng L, Ye P, Liu C. The role of the IL-23/IL-17 axis in the pathogenesis of Graves’ disease. Endocr J 2013;60:591-7
   PubMed Web of Science ®Google Scholar
• Cua DJ, Sherlock J, Chen Y, et al. Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain. Nature 2003;421:744-8
   PubMed Web of Science ®Google Scholar
• Murphy CA, Langrish CL, Chen Y, et al. Divergent pro- and antiinflammatory roles for IL-23 and IL-12 in joint autoimmune inflammation. J Exp Med 2003;198:1951-7
   PubMed Web of Science ®Google Scholar
• Langrish CL, Chen Y, Blumenschein WM, et al. IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Exp Med 2005;201:233-40
   PubMed Web of Science ®Google Scholar
• Bedoya SK, Lam B, Lau K, Larkin J 3rd. Th17 cells in immunity and autoimmunity. Clin Dev Immunol 2013;2013:986789
   PubMedGoogle Scholar
• Ogura H1, Murakami M, Okuyama Y, et al. Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction. Immunity 2008;29(4):628-36
   PubMed Web of Science ®Google Scholar
• Kim SE, Yoon JS, Kim KH, Lee SY. Increased serum interleukin-17 in Graves’ ophthalmopathy. Graefes Arch Clin Exp Ophthalmol 2012;250:1521-6
   Google Scholar
• Guo T, Huo Y, Zhu W, et al. Genetic association between IL-17F gene polymorphisms and the pathogenesis of Graves’ Disease in the Han Chinese population. Gene 2013;512:300-4
   Google Scholar
• Nanba T, Watanabe M, Inoue N, Iwatani Y. Increases of the Th1/Th2 cell ratio in severe Hashimoto’s disease and in the proportion of Th17 cells in intractable Graves’ disease. Thyroid 2009;19:495-501
   PubMed Web of Science ®Google Scholar
• Peng D, Xu B, Wang Y, et al. A high frequency of circulating th22 and th17 cells in patients with new onset Graves’ disease. PLoS One 2013;8:e68446
   Google Scholar
• Li JR, Hong FY, Zeng JY, Huang GL. Functional interleukin-17 receptor A are present in the thyroid gland in intractable Graves’ disease. Cell Immunol 2013;281:85-90
   PubMed Web of Science ®Google Scholar
• Wendling D, Racadot E, Wijdenes J. Treatment of severe rheumatoid arthritis by anti-interleukin 6 monoclonal antibody. J Rheumatol 1993;20:259-62
   PubMed Web of Science ®Google Scholar
• Yoshizaki K, Nishimoto N, Mihara M, Kishimoto T. Therapy of rheumatoid arthritis by blocking IL-6 signal transduction with a humanized anti-IL-6 receptor antibody. Springer Semin Immunopathol 1998;20:247-59
   PubMed Web of Science ®Google Scholar
• Navarro-Millán I, Singh JA, Curtis JR. Systematic review of tocilizumab for rheumatoid arthritis: a new biologic agent targeting the interleukin-6 receptor. Clin Ther 2012;34:788-802
   PubMed Web of Science ®Google Scholar
• Chaitow J, De Benedetti F, Brunner H, et al. Tocilizumab in patients with systemic juvenile idiopathic arthritis: efficacy data from the placebo-controlled 12-week part of the phase 3 TENDER Trial. Ann Rheum Dis 2010;69(Suppl 3):146
   Google Scholar
• Campbell L, Chen C, Bhagat SS, et al. Risk of adverse events including serious infections in rheumatoid arthritis patients treated with tocilizumab: systematic literature review and meta-analysis of randomized controlled trials. Rheumatology (Oxford) 2011;50:552-62
   PubMed Web of Science ®Google Scholar
• Singh JA, Beg S, Lopez-Olivo MA. Tocilizumab for rheumatoid arthritis: a Cochrane systematic review. J Rheumatol 2011;38:10-20
   PubMed Web of Science ®Google Scholar
• Maini R, St. Clair EW, Breedveld F, et al. Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 1999;354:1932-9
   PubMed Web of Science ®Google Scholar
• Bongartz T, Sutton AJ, Sweeting MJ, et al. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA 2006;295:2275-85
   PubMed Web of Science ®Google Scholar
• Grijalva CG, Chen L, Delzell E, et al. Initiation of tumor necrosis factor-α antagonists and the risk of hospitalization for infection in patients with autoimmune diseases. JAMA 2011;306:2331-9
   PubMed Web of Science ®Google Scholar
• Paridaens D, van den Bosch WA, van der Loos TL, et al. The effect of etanercept on Graves’ ophthalmopathy: a pilot study. Eye 2005;19:1286-9
   PubMed Web of Science ®Google Scholar
• Durrani OM, Reuser TQ, Murray PI. Infliximab: a novel treatment for sight-threatening thyroid associated ophthalmopathy. Orbit 2005;24:117-19
   PubMedGoogle Scholar
• Theodossiadis PG, Markomichelakis NN, Sfikakis PP. Tumor necrosis factor antagonists: preliminary evidence for an emerging approach in the treatment of ocular inflammation. Retina 2007;27:399-413
   PubMed Web of Science ®Google Scholar
• Van Lieshout AW, Creemers MC, Radstake TR, et al. Graves’ disease in a patient with rheumatoid arthritis during treatment with anti-tumor necrosis factor-alpha. J Rheumatol 2008;35:938-9
   Google Scholar
• Tektonidou MG, Anapliotou M, Vlachoyiannopoulos P, Moutsopoulos HM. Presence of systemic autoimmune disorders in patients with autoimmune thyroid diseases. Ann Rheum Dis 2004;63:1159-61
   PubMed Web of Science ®Google Scholar
• ClinicalTrials.gov. Available from: http://clinicaltrials.gov/show/NCT01868997
   Google Scholar
• Chiricozzi A, Krueger JG. IL-17 targeted therapies for psoriasis. Expert Opin Investig Drugs 2013;22:993-1005
   PubMed Web of Science ®Google Scholar
• Baeten D, Baraliakos X, Braun J, et al. Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial. Lancet 2013;382:1705-13
   PubMed Web of Science ®Google Scholar
• Eskan MA, Jotwan R, Abe T, et al. The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss. Nat Immunol 2012;13:465-74
   PubMed Web of Science ®Google Scholar
• Khader SA. Restraining IL-17: del-1 deals the blow. Nat Immunol 2012;13:433-5
   Google Scholar
• Firestein GS, Echeverri F, Yeo M, et al. Somatic mutations in the p53 tumor suppressor gene in rheumatoid arthritis synovium. Proc Natl Acad Sci U S A 1997;94:10895-900
   PubMed Web of Science ®Google Scholar
• Park JS, Lim MA, Cho ML, et al. p53 controls autoimmune arthritis via STAT-mediated regulation of the Th17 cell/Treg cell balance in mice. Arthritis Rheum 2013;65:949-59
   Google Scholar
• Hsieh CS, Macatonia SE, Tripp CS, et al. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science 1993;260:547-9
   PubMed Web of Science ®Google Scholar
• Gately MK, Wolitzky AG, Quinn PM, Chizzonite R. Regulation of human cytolytic lymphocyte responses by interleukin-12. Cell Immunol 1992;143:127-42
   PubMed Web of Science ®Google Scholar
• Benson JM, Peritt D, Scallon BJ, et al. Discovery and mechanism of ustekinumab: a human monoclonal antibody targeting interleukin-12 and interleukin-23 for treatment of immune-mediated disorders. MAbs 2011;3(6):535-45
   PubMed Web of Science ®Google Scholar
• Leonardi CL, Kimball AB, Papp KA, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-controlled trial (PHOENIX 1). Lancet 2008;371:1665-74
   PubMed Web of Science ®Google Scholar
• Sandborn WJ, Gasink C, Gao LL, et al. Ustekinumab induction and maintenance therapy in refractory Crohn’s disease. N Engl J Med 2012;367:1519-28
   PubMed Web of Science ®Google Scholar
• Yeilding N, Szapary P, Brodmerkel C, et al. Development of the IL-12/23 antagonist ustekinumab in psoriasis: past, present, and future perspectives--an update. Ann N Y Acad Sci 2012;1263:1-12
   PubMed Web of Science ®Google Scholar
• Nakajima K, Kanda T, Takaishi M, et al. Distinct roles of IL-23 and IL-17 in the development of psoriasis-like lesions in a mouse model. J Immunol 2011;186:4481-9
   PubMed Web of Science ®Google Scholar
• Chen Y, Langrish CL, McKenzie B, et al. Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J Clin Invest 2006;116:1317-26
   PubMed Web of Science ®Google Scholar
• Levin AA, Gottlieb AB. Specific targeting of interleukin-23p19 as effective treatment for psoriasis. J Am Acad Dermatol 2014;70:555-61
   PubMed Web of Science ®Google Scholar
• Fischer M1, Ehlers M. Toll-like receptors in autoimmunity. Ann N Y Acad Sci 2008;1143:21-34
   PubMed Web of Science ®Google Scholar
• Jiang W, Zhu FG, Bhagat L, et al. A Toll-like receptor 7, 8, and 9 antagonist inhibits Th1 and Th17 responses and inflammasome activation in a model of IL-23-induced psoriasis. J Invest Dermatol 2013;133(7):1777-84
   PubMed Web of Science ®Google Scholar
• Salvi M. Rituximab in Graves’ ophthalmopathy. Presented at American Thyroid Association; San Juan, Puerto Rico, USA; 2013
   Google Scholar
• Stan MN, Garrity JA, Thapa P, et al. Randomized double-blind placebo-controlled trial of rituximab for treatment of Graves’ ophthalmopathy. Presented at American Thyroid Association; San Juan, Puerto Rico, USA; 2013
   Google Scholar
• El Fassi D, Nielsen CH, Bonnema SJ, et al. B lymphocyte depletion with the monoclonal antibody rituximab in Graves’ disease: a controlled pilot study. J Clin Endocrinol Metab 2007;92:1769-72
   PubMed Web of Science ®Google Scholar
• Salvi M, Vannucchi G, Campi I, et al. Treatment of Graves’ disease and associated ophthalmopathy with the anti-CD20 monoclonal antibody rituximab: an open study. Eur J Endocrinol 2007;156:33-40
   PubMed Web of Science ®Google Scholar
• Heemstra KA, Toes RE, Sepers J, et al. Rituximab in relapsing Graves’ disease, a phase II study. Eur J Endocrinol 2008;159:609-15
   PubMed Web of Science ®Google Scholar
• Khanna D, Chong KK, Afifiyan NF, et al. Rituximab treatment of patients with severe, corticosteroid-resistant thyroid-associated ophthalmopathy. Ophthalmology 2010;117:133-9
   PubMed Web of Science ®Google Scholar
• Silkiss RZ, Reier A, Coleman M, Lauer SA. Rituximab for thyroid eye disease. Ophthal Plast Reconstr Surg 2010;26:310-14
   PubMed Web of Science ®Google Scholar