Summary:
Autoimmune thyroid disease is the most common organ-specific autoimmune disease and is a very common cause of thyroid dysfunction such as autoimmune hypothyroidism, Graves' disease and postpartum thyroiditis. The thyroid gland from patients with autoimmune thyroid disease is morphologically characterized by massive infiltration of lymphoid cells. The interleukin-1 (IL-1) family of molecules is together with other cytokines an integral component of the complex intercellular communication required to mount and control an immune response.
IL-1α/β in moderate and high concentrations reversibly inhibit thyroid cell function, while IL-1β in low concentrations stimulates thyroid cell function. The biphasic, non-cytotoxic and reversible influence of IL-1 supports a role of IL-1 in the physiological regulation of thyroid cell function. IL-1 stimulates the guanylate mediated pathways and inhibits the adenylate cyclase mediated pathways. All IL-1 effects are counteracted by IL-1 receptor antagonist indicating that the effects are exerted through activation of specific IL-1 receptors on thyrocytes. Furthermore, IL-1 induces or enhances expression of a number of immunologically active molecules such as adhesion molecules, cytokines, and complement regulatory proteins in thyroid epithelial cells. IL-1 may thus play a role during physiological as well as pathophysiological conditions contributing to for example the euthyroid sick syndrome and development of thyroid autoimmunity.
This review summarizes current litterature on the phenomenological in vitro influence of IL-1 on the thyroid cell.
Abbreviations: cAMP: cyclic adenylate monophosphate, cGMP: cyclic guanylate monophosphate, FRTL: Fischer rat thyroid line, ICAM: intercellular adhesion molecule, IL-1: interleukin-1, IL-6: interleukin-6, IL-8: interleukin-8, IL-1RA: Interleukin-1 receptor antagonist, L-NMMA: L-NG-monomethyl-arginine, NIS: Na+/I- symporter, NO: nitric oxide, rh: recombinant human, TEC: thyroid epithelial cells, Tg: thyroglobulin, TPO: thyroid peroxidase, TSH: thyrotropin
Key words:
Autoimmune thyroid disease - thyrocytes - interleukin-1 - interleukin-1 receptor antagonist
References
-
1
Ajjan R A, Watson P F, Findlay C, Metcalfe R A, Crisp M, Ludgate M, Weetman A P.
The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity.
J Endocrinol.
158
351-358
1998;
-
2
Asakawa H, Hanafusa T, Oda Y, Katsura H, Miyagawa J-I, Mashita K, Kono N, Tarui S.
Human recombinant interleukin 1 inhibits TSH-stimulated morphological changes in thyroid follicles cultured as semi-organs.
Acta Endocrinol (Copenh).
125
80-85
1991;
-
3
Asakawa H, Miyagawa J-I, Kobayashi T, Hanafusa T, Kuwajima M, Matsuzawa Y.
Effects of interleukin-1γβ on scanning electron microscopic appearance and thyroid peroxidase content of human thyrocytes in monolayer culture.
Immunopharm.
34
131-137
1996;
-
4
Ashizawa K, Yamashita S, Tobinga T, Nagayama Y, Kimura H, Hirayu H, Izumi M, Nagataki S.
Inhibition of human thyroid peroxidase gene expression by interleukin 1.
Acta Endocrinol (Copenh).
121
465-469
1989;
-
5
Bendtzen K.
Cytokines and natural regulators of cytokines.
Immunol Lett.
43
111-123
1994;
-
6
Bendtzen K.
Immune hormones (cytokines); pathogenic role in autoimmune rheumatic diseases and endocrine diseases.
Autoimmunity.
2
177-189
1989;
-
7
Bendtzen K, Rasmussen Å K, Bech K, Feldt-Rasmussen U, Buschard K.
Pathogenic role of interleukin 1 and tumor necrosis factor in autoimmune endocrine diseases.
Clin Immunol Newlet.
9
72-74
1988;
-
8
Borgerson K L, Bretz J D, Baker J R.
The role of Fas-mediated apoptosis in thyroid autoimmune disease.
Autoimmunity.
30
251-264
1999;
-
9
Diamant M, Kayser L, Rasmussen Å K, Bendtzen K.
Interleukin-6 production by thyroid epithelial cells. Enhancement by interleukin-1.
Autoimmunity.
11
21-26
1991;
-
10
Estevez R, van Sande J, Dumont J.
Nitric oxide as a signal in thyroid.
Mol Cell Endocrinol.
90
R1-R3
1992;
-
11
Kasai K, Hattori Y, Nakanishi N, Manaka K, Banba N, Motohashi S, Shimoda S-I.
Regulation of inducible nitric oxide production by cytokines in human thyrocytes in culture.
Endocrinol.
136
4261-4270
1995;
-
12
Kasai K, Hiraiwa M, Emoto T, Kuroda Y, Hattori Y, Mochizuki Y, Nakamura T, Shimoda S-I.
Presence of high affinity receptor for interleukin-1 (IL-1) on cultured porcine thyroid cells.
Horm Metabol Res.
22
75-79
1990;
-
13
Kawabe Y, Eguchi K, Shimomura C, Mine M, Otsubo T, Ueki Y, Tezuka H, Nakao H, Kawakami A, Migita K, Yamashita S, Matsunaga A, Ishikawa N, Ito K, Nagataki S.
Interleukin-1 production and action in thyroid tissue.
J Clin Endocrinol Metab.
68
1174-1183
1989;
-
14
Kennedy R L, Jones T H.
Cytokines in endocrinology: their roles in health and in disease.
J Endocrinol.
129
167-178
1991;
-
15
Kennedy R L, Jones T H, Davies R, Justice S K, Lemoine N R.
Release of interleukin-6 by human thyroid epithelial cells immortalized by simian virus 40 DNA transfection.
J Endocrinol.
133
477-482
1992;
-
16
Kimura H, Yamashita S, Namba H, Tominaga T, Tsuruta M, Yokoyama N, Izumi M, Nagataki S.
Interleukin-1 inhibits human thyroid carcinoma cell growth.
J Clin Endocrinol Metab.
75
596-602
1992;
-
17
Kung A W, Lau K S.
Interleukin-1 beta modulates thyrotropin-induced thyroglobulin mRNA transcription through 3′,5′-cyclic adenosine monophosphate.
Endocrinol.
127
1369-1374
1990;
-
18
Millatt L J, Jackson R, Williams B C, Whitley G StJ.
Nitric oxide stimulates cyclic GMP in human thyrocytes.
J Mol Endocrinol.
10
163-169
1993;
-
19
Mine M, Tramontano D, Chin W C, Ingbar S H.
Interleukin 1 stimulates thyroid cell growth and increases the concentration of the c-myc proto-oncogene mRNA in thyroid follicular cells in culture.
Endocrinol.
120
1212-1214
1987;
-
20
Nilsson M, Husmark J, Bjorkman U, Ericson L E.
Cytokines and thyroid epithelial integrity: interleukin-1 alpha induces dissociation of the junctional complex and paracellular leakage in filter-cultured human thyrocytes.
J Clin Endocrinol Metab.
83
945-952
1998;
-
21
Pang X-P, Hershman J M, Smith V, Pekary A E, Sugawara M.
The mechanism of action of tumor necrosis factor-γα and interleukin-1 on FRTL-5 cells.
Acta Endocrinol (Copenh).
123
203-210
1990;
-
22
Paolieri F, Salmaso C, Battifora M, Montagna P, Pesce G, Bagnasco M, Richiusa P, Galluzzo A, Giordano C.
Possible pathogenetic relevance of interleukin-1 beta in “destructive” organ-specific autoimmune disease (Hashimoto's thyroiditis).
Ann N Y Acad Sci.
876
221-228
1999;
-
23
Pekary A E, Berg L, Santini F, Chopra I, Hershman J M.
Cytokines modulate type I iodothyronine deiodinase mRNA levels and enzyme activity in FRTL-5 rat thyroid cells.
Mol Cell Endocrinol.
101
R31-R35
1994;
-
24
Rasmussen Å K, Bech K, Feldt-Rasmussen U, Poulsen S, Holten I, Ryberg M, Dinarello C A, Siersbæk-Nielsen K, Friis T, Bendtzen K.
Interleukin-1β affects the function of cultured human thyroid cells.
Allergy.
43
435-441
1988;
-
25
Rasmussen Å K, Diamant M, Blichert-Toft M, Bendtzen K, Feldt-Rasmussen U.
The effects of interleukin (IL)-1γβ on human thyrocyte functions are counteracted by the IL-1 receptor antagonist.
Endocrinol.
138
2043-2048
1997;
-
26
Rasmussen Å K, Di Marco R, Diamant M, Feldt-Rasmussen U, Bendtzen K.
Nitric oxide production is not involved in the effects of interleukin-1γβ on cAMP, thyroglobulin and interleukin-6 in TSH-stimulated human thyroid cells.
Autoimmunity.
19
239-245
1994;
, (Authors' Corrigendum in Autoimmunity 23: 289, 1996)
-
27
Rasmussen Å K, Kayser L, Bech K, Feldt-Rasmussen U, Perrild H, Bendtzen K.
Differential effects of interleukin 1γα and 1β on cultured human and rat thyroid cells.
Acta Endocrinol.
122
520-526
1990;
-
28
Reimers J, Rasmussen Å K, Karlsen A E, Bjerre U, Liang H, Morin O, Andersen H U, Mandrup-Poulsen T, Burger A, Feldt-Rasmussen U, Nerup J.
Interleukin-1γβ inhibits rat thyroid cell function in vivo and in vitro by an NO independent mechanism and induces hypothyroidism and accelerated thyroiditis in diabetes-prone BB rats.
J Endocrinol.
151
147-157
1996;
-
29
Sato K, Satoh T, Shizume K, Ozawa M, Han D C, Imamura H, Tsushima T, Demura H, Kanaji Y, Ito Y, Obara T, Fujimoto Y, Kanaji Y.
Inhibition of 125I organification and thyroid hormone release by interleukin-1, tumor necrosis factor-γα, and interferon-γγ in human thyrocytes in suspension culture.
J Clin Endocrinol Metab.
70
1735-1743
1990;
-
30
Shong M, Ro H K, Kim Y K, Yoo C J, Lee J H, Song C U, Cho B Y.
The cytokines, interleukin-1γβ interleukin-6 and interferon-γγ upregulate the expression of intercellular adhesion molecule-1 (ICAM-1) in rat thyroid cell line, FRTL-5.
Kor J Int Med.
9
88-92
1994;
-
31
Svenson M, Hansen M B, Kayser L, Rasmussen Å K, Reimert C M, Bendtzen K.
Effects of human anti-IL-1γα autoantibodies on receptor binding and biological activities of IL-1.
Cytokine.
4
125-133
1992;
-
32
Svenson M, Kayser L, Hansen M B, Rasmussen Å K, Bendtzen K.
Interleukin 1 receptor on human thyroid cells and on the rat thyroid cell line FRTL 5.
Cytokine.
3
125-130
1991;
-
33
Tandon N, Dinsdale C, Tamatani T, Miyasaka M, Weetman A P.
Adhesion molecule expression by the FRTL-5 rat thyroid cell line.
J Endocrinol.
130
451-456
1991;
-
34
Tandon N, Morgan B P, Weetman A P.
Expression and function of membrane attack complex inhibitory proteins on thyroid follicular cells.
Immunol.
75
372-377
1992;
-
35
Tolosa E, Roura C, Martí M, Belfiore A, Pujol-Borrell R.
Induction of intercellular adhesion molecule-1 but not of lymphocyte function-associated antigen-3 in thyroid follicular cells.
J Autoimmun.
5
119-135
1992;
-
36
Watson P F, Pickerill A P, Davies R, Weetman A P.
Semi-quantitative analysis of interleukin-1γα, interleukin-6 and interleukin-8 mRNA expression by human thyrocytes.
J Mol Endocrinol.
15
11-21
1995;
-
37
Weetman A P, Ajjan R A, Watson P F.
Cytokines and Graves' disease.
Baillière's Clin Endocrinol Metab.
11
481-497
1997;
-
38
Weetman A P, Bennett G L, Wong W LT.
Thyroid follicular cells produce interleukin-8.
J Clin Endocrinol Metab.
75
328-330
1992 a;
-
39
Weetman A P, Cohen S, Makgoba M W, Borysiewicz L K.
Expression of an intercellular adhesion molecule, ICAM-1, by human thyroid cells.
J Endocrinol.
122
185-191
1989;
-
40
Weetman A P, Freeman M, Morgan B P.
Thyroid follicular cell function after non-lethal complement membrane attack.
Clin Exp Immunol.
82
69-74
1990;
-
41
Weetman A P, Tandon N, Morgan B P.
Antithyroid drugs and release of inflammatory mediators by complement-attacked thyroid cells.
Lancet.
340
633-636
1992 b;
-
42
Yamashita S, Kimura K, Ashizawa Y, Nagayama Y, Hiraya H, Izumi M, Nagataki S.
Interleukin-1 inhibits thyrotropin-induced human thyroglobulin gene expression.
J Endocrinol.
122
177-183
1989;
-
43
Yip I, Pang X-P, Berg L, Hershman J M.
Antitumor actions of interferon-γγ and interleukin-1γβ on human papillary thyroid carcinoma cell lines.
J Clin Endocrinol Metab.
80
1664-1669
1995;
-
44
Zeki K, Azuma H, Suzuki H, Morimoto I, Eto S.
Effects of interleukin 1 on growth and adenosine 3′,5′-monophosphate generation of the rat thyroid cell line FRTL5 cells.
Acta Endocrinol (Copenh).
124 (1)
60-66
1991;
-
45
Zeki K, Nakano Y, Inokuchi N, Watanabe K, Morimoto I, Yamashita U, Eto S.
Autocrine stimulation of interleukin-1 in the growth of human thyroid carcinoma cell line NIM1.
J Clin Endocrinol Metab.
76
127-133
1993;
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