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Published in: Graefe's Archive for Clinical and Experimental Ophthalmology 10/2012

01-10-2012 | Oculoplastics and Orbit

Increased serum interleukin-17 in Graves’ ophthalmopathy

Authors: Sung Eun Kim, Jin Sook Yoon, Keun Ho Kim, Sang Yeul Lee

Published in: Graefe's Archive for Clinical and Experimental Ophthalmology | Issue 10/2012

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Abstract

Background

Interleukin (IL)-17 and T helper 17 (Th17) cells are reported to be involved in many autoimmune diseases. The aim of this study is to investigate the involvement of IL-17 in the pathogenesis and disease activity of Graves’ ophthalmopathy (GO).

Methods

Sixty-two GO patients and 19 healthy controls were recruited. Serum concentrations of cytokines, IL-17, IL-6, IL-23, and IL-16, were measured using multiplexed microsphere-based flow cytometric immunoassays. GO hormonal parameters, clinical activity score (CAS), exophthalmometry, and extraocular muscle involvement were evaluated, and relationships with cytokine concentrations were analyzed.

Results

The concentration and positive detection rates of serum IL-17 were significantly higher in patients with GO than in controls. The serum levels of IL-17 in active GO patients were higher than that of inactive GO patients. Serum IL-17 concentration had significant correlation with CAS (p < 0.001).

Conclusion

The increased serum level of IL-17 and related cytokines in GO patients and the correlation of IL-17 concentration with the clinical activity scores suggest that IL-17 may play a pathophysiological role in GO.
Literature
2.
go back to reference Gianoukakis AG, Khadavi N, Smith TJ (2008) Cytokines, Graves' disease, and thyroid-associated ophthalmopathy. Thyroid 18:953–958PubMedCrossRef Gianoukakis AG, Khadavi N, Smith TJ (2008) Cytokines, Graves' disease, and thyroid-associated ophthalmopathy. Thyroid 18:953–958PubMedCrossRef
3.
go back to reference Ziolkowska M, Koc A, Luszczykiewicz G, Ksiezopolska-Pietrzak K, Klimczak E, Chwalinska-Sadowska H, Maslinski W (2000) High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. J Immunol 164:2832–2838PubMed Ziolkowska M, Koc A, Luszczykiewicz G, Ksiezopolska-Pietrzak K, Klimczak E, Chwalinska-Sadowska H, Maslinski W (2000) High levels of IL-17 in rheumatoid arthritis patients: IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism. J Immunol 164:2832–2838PubMed
4.
go back to reference Kryczek I, Bruce AT, Gudjonsson JE, Johnston A, Aphale A, Vatan L, Szeliga W, Wang Y, Liu Y, Welling TH, Elder JT, Zou W (2008) Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol 181:4733–4741PubMed Kryczek I, Bruce AT, Gudjonsson JE, Johnston A, Aphale A, Vatan L, Szeliga W, Wang Y, Liu Y, Welling TH, Elder JT, Zou W (2008) Induction of IL-17+ T cell trafficking and development by IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol 181:4733–4741PubMed
5.
go back to reference Nalbandian A, Crispin JC, Tsokos GC (2009) Interleukin-17 and systemic lupus erythematosus: current concepts. Clin Exp Immunol 157:209–215PubMedCrossRef Nalbandian A, Crispin JC, Tsokos GC (2009) Interleukin-17 and systemic lupus erythematosus: current concepts. Clin Exp Immunol 157:209–215PubMedCrossRef
6.
go back to reference Mills KH (2008) Induction, function and regulation of IL-17-producing T cells. Eur J Immunol 38:2636–2649PubMedCrossRef Mills KH (2008) Induction, function and regulation of IL-17-producing T cells. Eur J Immunol 38:2636–2649PubMedCrossRef
7.
go back to reference Ouyang W, Kolls JK, Zheng Y (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28:454–467PubMedCrossRef Ouyang W, Kolls JK, Zheng Y (2008) The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28:454–467PubMedCrossRef
8.
go back to reference Huber AK, Jacobson EM, Jazdzewski K, Concepcion ES, Tomer Y (2008) Interleukin (IL)-23 receptor is a major susceptibility gene for Graves' ophthalmopathy: the IL-23/T-helper 17 axis extends to thyroid autoimmunity. J Clin Endocrinol Metab 93:1077–1081PubMedCrossRef Huber AK, Jacobson EM, Jazdzewski K, Concepcion ES, Tomer Y (2008) Interleukin (IL)-23 receptor is a major susceptibility gene for Graves' ophthalmopathy: the IL-23/T-helper 17 axis extends to thyroid autoimmunity. J Clin Endocrinol Metab 93:1077–1081PubMedCrossRef
9.
go back to reference Chen Y, Langrish CL, McKenzie B, Joyce-Shaikh B, Stumhofer JS, McClanahan T, Blumenschein W, Churakovsa T, Low J, Presta L, Hunter CA, Kastelein RA, Cua DJ (2006) Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J Clin Invest 116:1317–1326PubMedCrossRef Chen Y, Langrish CL, McKenzie B, Joyce-Shaikh B, Stumhofer JS, McClanahan T, Blumenschein W, Churakovsa T, Low J, Presta L, Hunter CA, Kastelein RA, Cua DJ (2006) Anti-IL-23 therapy inhibits multiple inflammatory pathways and ameliorates autoimmune encephalomyelitis. J Clin Invest 116:1317–1326PubMedCrossRef
10.
go back to reference Figueroa-Vega N, Alfonso-Perez M, Benedicto I, Sanchez-Madrid F, Gonzalez-Amaro R, Marazuela M (2010) Increased circulating pro-inflammatory cytokines and Th17 lymphocytes in Hashimoto's thyroiditis. J Clin Endocrinol Metab 95:953–962PubMedCrossRef Figueroa-Vega N, Alfonso-Perez M, Benedicto I, Sanchez-Madrid F, Gonzalez-Amaro R, Marazuela M (2010) Increased circulating pro-inflammatory cytokines and Th17 lymphocytes in Hashimoto's thyroiditis. J Clin Endocrinol Metab 95:953–962PubMedCrossRef
11.
go back to reference Horie I, Abiru N, Saitoh O, Ichikawa T, Iwakura Y, Eguchi K, Nagayama Y (2011) Distinct role of T helper Type 17 immune response for Graves' hyperthyroidism in mice with different genetic backgrounds. Autoimmunity 44:159–165PubMedCrossRef Horie I, Abiru N, Saitoh O, Ichikawa T, Iwakura Y, Eguchi K, Nagayama Y (2011) Distinct role of T helper Type 17 immune response for Graves' hyperthyroidism in mice with different genetic backgrounds. Autoimmunity 44:159–165PubMedCrossRef
12.
go back to reference Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, Curro N, Daumerie C, Kahaly GJ, Krassas GE, Lane CM, Lazarus JH, Marino M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM (2008) Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 158:273–285PubMedCrossRef Bartalena L, Baldeschi L, Dickinson A, Eckstein A, Kendall-Taylor P, Marcocci C, Mourits M, Perros P, Boboridis K, Boschi A, Curro N, Daumerie C, Kahaly GJ, Krassas GE, Lane CM, Lazarus JH, Marino M, Nardi M, Neoh C, Orgiazzi J, Pearce S, Pinchera A, Pitz S, Salvi M, Sivelli P, Stahl M, von Arx G, Wiersinga WM (2008) Consensus statement of the European Group on Graves' orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 158:273–285PubMedCrossRef
13.
go back to reference Mazzoccoli G, Carughi S, Sperandeo M, Pazienza V, Giuliani F, Tarquini R (2011) Neuro-endocrine correlations of hypothalamic–pituitary–thyroid axis in healthy humans. J Biol Regul Homeost Agents 25:249–257PubMed Mazzoccoli G, Carughi S, Sperandeo M, Pazienza V, Giuliani F, Tarquini R (2011) Neuro-endocrine correlations of hypothalamic–pituitary–thyroid axis in healthy humans. J Biol Regul Homeost Agents 25:249–257PubMed
14.
go back to reference Aziz NA, Pijl H, Frolich M, Roelfsema F, Roos RA (2011) Diurnal secretion profiles of growth hormone, thyrotrophin and prolactin in Parkinson's disease. J Neuroendocrinol 23:519–524PubMedCrossRef Aziz NA, Pijl H, Frolich M, Roelfsema F, Roos RA (2011) Diurnal secretion profiles of growth hormone, thyrotrophin and prolactin in Parkinson's disease. J Neuroendocrinol 23:519–524PubMedCrossRef
15.
16.
go back to reference Wong CK, Lit LC, Tam LS, Li EK, Wong PT, Lam CW (2008) Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol 127:385–393PubMedCrossRef Wong CK, Lit LC, Tam LS, Li EK, Wong PT, Lam CW (2008) Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol 127:385–393PubMedCrossRef
17.
go back to reference Nanba T, Watanabe M, Inoue N, Iwatani Y (2009) Increases of the Th1/Th2 cell ratio in severe Hashimoto's disease and in the proportion of Th17 cells in intractable Graves' disease. Thyroid 19:495–501PubMedCrossRef Nanba T, Watanabe M, Inoue N, Iwatani Y (2009) Increases of the Th1/Th2 cell ratio in severe Hashimoto's disease and in the proportion of Th17 cells in intractable Graves' disease. Thyroid 19:495–501PubMedCrossRef
18.
go back to reference Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, Levy DE, Leonard WJ, Littman DR (2007) IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8:967–974PubMedCrossRef Zhou L, Ivanov II, Spolski R, Min R, Shenderov K, Egawa T, Levy DE, Leonard WJ, Littman DR (2007) IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways. Nat Immunol 8:967–974PubMedCrossRef
19.
20.
go back to reference Kikly K, Liu L, Na S, Sedgwick JD (2006) The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol 18:670–675PubMedCrossRef Kikly K, Liu L, Na S, Sedgwick JD (2006) The IL-23/Th(17) axis: therapeutic targets for autoimmune inflammation. Curr Opin Immunol 18:670–675PubMedCrossRef
Metadata
Title
Increased serum interleukin-17 in Graves’ ophthalmopathy
Authors
Sung Eun Kim
Jin Sook Yoon
Keun Ho Kim
Sang Yeul Lee
Publication date
01-10-2012
Publisher
Springer-Verlag
Published in
Graefe's Archive for Clinical and Experimental Ophthalmology / Issue 10/2012
Print ISSN: 0721-832X
Electronic ISSN: 1435-702X
DOI
https://doi.org/10.1007/s00417-012-2092-7

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