RSS-Feed abonnieren
DOI: 10.1055/s-0032-1308973
Elevated Serum IL-16 and RANTES Levels in Patients with Autoimmune Thyroid Diseases and Modulation by Methimazole Therapy
Publikationsverlauf
received 23. Dezember 2011
accepted 01. März 2012
Publikationsdatum:
02. April 2012 (online)
![](https://www.thieme-connect.de/media/hmr/201206/lookinside/thumbnails/10.1055-s-0032-1308973-1.jpg)
Abstract
Interleukine-16 (IL-16) and RANTES (regulated upon activation, normal T cell expressed and secreted) are 2 cytokines with the function of T helper cell recruitment, which might play a key role in pathogenesis of autoimmune thyroid diseases (AITD). This study was aimed to evaluate the IL-16 and RANTES in patients with AITD. Serum IL-16 and RANTES levels were measured in patients with Graves’ disease (GD; n=45), Hashimoto’s thyroiditis (HT; n=68), nontoxic multinodular goiter (NTMNG; n=20), and healthy individuals (n=61). The results showed that serum IL-16 and RANTES levels were elevated both in HT and higher in untreated GD patients when compared to NTMNG patients and the healthy individuals, which were decreased after MMI therapy in untreated GD patients. However, in HT patients, serum IL-16 and RANTES levels were comparable among the conditions of hyperthyroid and euthyroid received by l-thyroxine therapy and untreated hypothyroid. Furthermore, serum IL-16 levels were correlated with FT3, FT4, TRAb in GD, but not in HT patients. The data did not show any correlation between RANTES levels and clinical factors. In conclusion, IL-16 and RANTES might be involved in the pathogenesis of GD and HT, and serum IL-16 levels in GD maybe a potential marker of disease activity and severity.
-
References
- 1 Tezuka H, Eguchi K, Fukuda T, Otsubo T, Kawabe Y, Ueki Y, Matsunaga M, Shimomura C, Nakao H, Ishikawa N, Ito K, Nagataki S. Natural killer and natural killer-like cell activity of peripheral blood and intrathyroidal mononuclear cells from patients with Graves’ disease. J Clin Endocrinol Metab 1988; 66: 702-707
- 2 Weetman AP. Cellular immune responses in autoimmune thyroid disease. Clin Endocrinol (Oxf) 2004; 61: 405-413
- 3 Moser B, Wolf M, Walz A, Loetscher P. Chemokines: multiple levels of leukocyte migration control. Trends Immunol 2004; 25: 75-84
- 4 Schall TJ, Bacon K, Toy KJ, Goeddel DV. Selective attraction of monocytes and T lymphocytes of the memory phenotype by cytokine RANTES. Nature 1990; 347: 669-671
- 5 Berman JS, Cruikshank WW, Center DM, Theodore AC, Beer DJ. Chemoattractant lymphokines specific for the helper/inducer T-lymphocyte subset. Cell Immunol 1985; 95: 105-112
- 6 Cruikshank WW, Berman JS, Theodore AC, Bernardo J, Center DM. Lymphokine activation of T4+ T lymphocytes and monocytes. J Immunol 1987; 138: 3817-3823
- 7 Rand TH, Cruikshank WW, Center DM, Weller PF. CD4-mediated stimulation of human eosinophils: lymphocyte chemoattractant factor and other CD4-binding ligands elicit eosinophil migration. J Exp Med 1991; 173: 1521-1528
- 8 Laberge S, Cruikshank WW, Kornfeld H, Center DM. Histamine-induced secretion of lymphocyte chemoattractant factor from CD8+ T cells is independent of transcription and translation. Evidence for constitutive protein synthesis and storage. J Immunol 1995; 155: 2902-2910
- 9 Lim KG, Wan HC, Bozza PT, Resnick MB, Wong DT, Cruikshank WW, Kornfeld H, Center DM, Weller PF. Human eosinophils elaborate the lymphocyte chemoattractants. IL-16 (lymphocyte chemoattractant factor) and RANTES. J Immunol 1996; 156: 2566-2570
- 10 Sciaky D, Brazer W, Center DM, Cruikshank WW, Smith TJ. Cultured human fibroblasts express constitutive IL-16 mRNA: cytokine induction of active IL-16 protein synthesis through a caspase-3-dependent mechanism. J Immunol 2000; 164: 3806-3814
- 11 Gianoukakis AG, Martino LJ, Horst N, Cruikshank WW, Smith TJ. Cytokine-induced lymphocyte chemoattraction from cultured human thyrocytes: evidence for interleukin-16 and regulated upon activation, normal T cell expressed, and secreted expression. Endocrinology 2003; 144: 2856-2864
- 12 Bellini A, Yoshimura H, Vittori E, Marini M, Mattoli S. Bronchial epithelial cells of patients with asthma release chemoattractant factors for T lymphocytes. J Allergy Clin Immunol 1993; 92: 412-424
- 13 Franz JK, Kolb SA, Hummel KM, Lahrtz F, Neidhart M, Aicher WK, Pap T, Gay RE, Fontana A, Gay S. Interleukin-16, produced by synovial fibroblasts, mediates chemoattraction for CD4+ T lymphocytes in rheumatoid arthritis. Eur J Immunol 1998; 28: 2661-2671
- 14 Lee S, Kaneko H, Sekigawa I, Tokano Y, Takasaki Y, Hashimoto H. Circulating interleukin-16 in systemic lupus erythematosus. Br J Rheumatol 1998; 37: 1334-1337
- 15 Seegert D, Rosenstiel P, Pfahler H, Pfefferkorn P, Nikolaus S, Schreiber S. Increased expression of IL-16 in inflammatory bowel disease. Gut 2001; 48: 326-332
- 16 Pritchard J, Horst N, Cruikshank W, Smith TJ. Igs from patients with Graves’ disease induces the expression of T cell chemoattractants in their fibroblasts. J Immunol 2002; 168: 942-950
- 17 Gianoukakis AG, Douglas RS, King CS, Cruikshank WW, Smith TJ. Immunoglobulin G from patients with Graves’ disease induces interleukin-16 and RANTES expression in cultured human thyrocytes: a putative mechanism for T-cell infiltration of the thyroid in autoimmune disease. Endocrinology 2006; 147: 1941-1949
- 18 Gu XJ, Cui B, Zhao ZF, Chen HY, Li XY, Wang S, Ning G, Zhao YJ. Association of the interleukin (IL)-16 gene polymorphisms with Graves’ disease. Clin Immunol 2008; 127: 298-302
- 19 Matsushita M, Hayashi T, Ando S, Sekigawa I, Iida N, Hashimoto H, Hirose S. Changes of CD4/CD8 ratio and interleukin-16 in systemic lupus erythematosus. Clin Rheumatol 2000; 19: 270-274
- 20 Wu KG, Li TH, Chen CJ, Cheng HI, Wang TY. Correlations of serum Interleukin-16, total IgE, eosinophil cationic protein and total eosinophil counts with disease activity in children with atopic dermatitis. Int J Immunopathol Pharmacol 2011; 24: 15-23
- 21 Salvi M, Pedrazzoni M, Girasole G, Giuliani N, Minelli R, Wall JR, Roti E. Serum concentrations of proinflammatory cytokines in Graves’ disease: effect of treatment, thyroid function, ophthalmopathy and cigarette smoking. Eur J Endocrinol 2000; 143: 197-202
- 22 Antonelli A, Rotondi M, Fallahi P, Romagnani P, Ferrari SM, Barani L, Ferrannini E, Serio M. Increase of interferon-gamma-inducible CXC chemokine CXCL10 serum levels in patients with active Graves’ disease, and modulation by methimazole therapy. Clin Endocrinol (Oxf) 2006; 64: 189-195
- 23 Lakatos P, Foldes J, Horvath C, Kiss L, Tatrai A, Takacs I, Tarjan G, Stern PH. Serum interleukin-6 and bone metabolism in patients with thyroid function disorders. J Clin Endocrinol Metab 1997; 82: 78-81
- 24 Siddiqi A, Monson JP, Wood DF, Besser GM, Burrin JM. Serum cytokines in thyrotoxicosis. J Clin Endocrinol Metab 1999; 84: 435-439
- 25 Fabris M, Grimaldi F, Villalta D, Picierno A, Fabro C, Bolzan M, De Vita S, Tonutti E. BLyS and April serum levels in patients with autoimmune thyroid diseases. Autoimmun Rev 2010; 9: 165-169
- 26 Koukkou E, Panayiotidis P, Alevizou-Terzaki V, Thalassinos N. High levels of serum soluble interleukin-2 receptors in hyperthyroid patients: correlation with serum thyroid hormones and independence from the etiology of the hyperthyroidism. J Clin Endocrinol Metab 1991; 73: 771-776
- 27 Nakamura H, Usa T, Motomura M, Ichikawa T, Nakao K, Kawasaki E, Tanaka M, Ishikawa K, Eguchi K. Prevalence of interrelated autoantibodies in thyroid diseases and autoimmune disorders. J Endocrinol Invest 2008; 31: 861-865
- 28 Pichler R, Maschek W, Hatzl-Griesenhofer M, Huber H, Crespillo-Gómez C, Berg J. Soluble tumour necrosis factor-alpha receptor I and interleukin-6 as markers of activity in thyrotoxic Graves’ disease. Horm Metab Res 2003; 35: 427-433
- 29 Díez JJ, Hernanz A, Medina S, Bayón C, Iglesias P. Serum concentrations of tumour necrosis factor-alpha (TNF-alpha) and soluble TNF-alpha receptor p55 in patients with hypothyroidism and hyperthyroidism before and after normalization of thyroid function. Clin Endocrinol (Oxf) 2002; 57: 515-521
- 30 Szyper-Kravitz M, Marai I, Shoenfeld Y. Coexistence of thyroid autoimmunity with other autoimmune diseases: friend or foe? Additional aspects on the mosaic of autoimmunity. Autoimmunity 2005; 38: 247-255
- 31 Kim H, Lee TH, Hwang YS, Bang MA, Kim KH, Suh JM, Chung HK, Yu DY, Lee KK, Kwon OY, Ro HK, Shong M. Methimazole as an antioxidant and immunomodulator in thyroid cells: mechanisms involving interferon-gamma signaling and H(2)O(2) scavenging. Mol Pharmacol 2001; 60: 972-980
- 32 Watson PF, Pickerill AP, Davies R, Weetman AP. Analysis of cytokine gene expression in Graves’ disease and multinodular goitre. J Clin Endocrinol Metab 1994; 79: 355-360
- 33 Crescioli C, Cosmi L, Borgogni E, Santarlasci V, Gelmini S, Sottili M, Sarchielli E, Mazzinghi B, Francalanci M, Pezzatini A, Perigli G, Vannelli GB, Annunziato F, Serio M. Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes. J Endocrinol 2007; 195: 145-155
- 34 Tsatsoulis A, Vlachoyiannopoulos PG, Dalekos GN, Johnson EO, Moutsopoulos HM. Increased serum interleukin-1 beta during treatment of hyperthyroidism with antithyroid drugs. Eur J Clin Invest 1995; 25: 654-658