Abstract
Autoimmune thyroid diseases are thought to be mediated by pro-inflammatory cytokines
such as TNFα and IL-6. Serum levels of cytokines may indicate activity levels of immune
functions. We investigated serum levels of IL-6 and of the soluble receptor of TNFα
in patients with newly diagnosed onset of Graves' hyperthyroidism. The predominantly
female group consisted of 39 patients, mean fT4 was 47.6 pg/ml (normal values 7.5
- 19.0 pg/ml). After diagnosis, all patients were treated with anti-thyroid drugs.
Soluble Tumour Necrosis Factor Receptor I (TNF-RI) serum levels were found significantly
increased (mean 3.7 ± 1.3 ng/ml; p < 0,01) compared to a matched group of apparent
healthy individuals (mean sTNF-RI 1.8 ± 0.5 ng/ml) and to a matched group of patients
with treated Graves' disease (mean sTNF-RI 1.9 ± 0.6 ng/ml). When IL-6 was assessed
only 4 of the 39 patients exhibited increased serum levels. Our finding may indicate
that sTNF-RI and possibly its ligand, TNFα, could play an important role in the onset
of the acute stage of Graves' disease.
Key words
TNF receptor - Cytokines - Hyperthyreosis - Graves' disease
References
- 1
Roura-Mir C, Catálfamo M, Sospedra M, Alcalde L, Pujol-Borrell R, Jaraquemada D.
Single-cell analysis of intrathyroidal lymphocytes shows differential cytokine expression
in Hashimoto's and Graves' disease.
Eur J Immunol.
1997;
27
3290-3302
- 2
Hunt P J, Marshall S E, Weetman A P, Bell J I, Wass J AH, Welsh K I.
Cytokine gene polymorphisms in autoimmune thyroid disease.
J Clin Endocrinol Metab.
2000;
85
1984-1988
- 3
Rasmussen A K, Hartoft-Nielsen M, Feldt-Rasmussen U.
Models to study the pathogenesis of thyroid autoimmunity.
Biochimie.
1999;
81
511-515
- 4
Ajjan R A, Watson P F, Weetman A P.
Cytokines and thyroid function.
Adv Neuroimmunol.
1996;
6
359-386
- 5
Aust G, Heuer M, Laue S, Lehmann I, Hofmann A, Heldin N E, Scherbaum W A.
Expression of tumour necrosis factor-alpha (TNF-alpha) mRNA and protein in pathological
thyroid tissue and carcinoma cell lines.
Clin Exp Immunol.
1996;
105
148-154
- 6
Nophar Y, Kemper O, Brakebush C, Englemann H, Zwang R, Aderka D, Holtmann H, Wallach D.
Soluble forms of human necrosis factor (TNF-Rs). The cDNA for the type I TNF-R, cloned
using amino acid sequence data of its soluble form encodes both the cell surface and
a soluble form of the receptor.
Eur Molec Biol Organ J.
1990;
9
3269-3273
- 7
Hohmann H P, Remy R, Brockhaus M, van Loon A PGM.
Two different cell types have different major receptors for human tumor necrosis factor
(TNF alpha).
J Biol Chem.
1989;
264
14 927-14 934
- 8
Pang X P, Yoshimura M, Hershman J M.
Suppression of rat thyrotroph and thyroid cell function by tumor necrosis factor-alpha.
Thyroid.
1993;
3
325-330
- 9
Siddiqi A, Monson J P, Wood D F, Besser G M, Burrin J M.
Serum cytokines in thyrotoxicosis.
J Clin Endocrinol Metab.
1999;
84
435-439
- 10
Salvi M, Pedrazzoni M, Girasole G, Giuliani N, Minelli R, Wall J R, Roti E.
Serum concentrations of proinflammatory cytokines in Graves's disease: effect of treatment,
thyroid function, ophthalmopathy and cigarette smoking.
Europ J Endocrinol.
2000;
143
197-202
- 11
Komiya I, Yamada T, Sato A, Kouki T, Nishimori T, Takasu N.
Remission and recurrence of hyperthyroid Graves' disease during and after methimazole
treatment when assessed by IgE and interleukin-13.
J Clin Endocrinol Metab.
2001;
86
3540-3544
- 12
Celik I, Akalin S, Erbas T.
Serum levels of interleukin 6 and tumor necrosis factor-alpha in hyperthyroid patients
before and after propylthiouracil treatment.
Eur J Endocrinol.
1995;
132
668-672
- 13
Akalin A, Colak Ö, Alatas Ö, Efe B.
Bone remodelling markers and serum cytokines in patients with hyperthyroidism.
Clin Endocrinol.
2002;
57
125-129
- 14
Lantz M, Malik S, Slevin M L, Olsson I.
Infusion of tumor necrosis factor (TNF) causes an increase in circulating TNF-binding
protein in humans.
Cytokine.
1990;
2
402-406
- 15
Diez-Ruiz A, Tilz G P, Zangerle R, Baier-Bitterlich G, Wachter H, Fuchs D.
Soluble receptors for tumour necrosis factor in clinical laboratory diagnosis.
Eur J Haematol.
1995;
54
1-8
- 16
Modzelewski B.
Release of tumor necrosis factor alfa and its soluble receptor p55 in clinical septic
syndrome.
Arch Immunol Ther Exp.
1997;
45
213-219
- 17
Bartalena L, Brogioni S, Grasso L, Martino E.
Increased serum interleukin-6 concentration in patients with subacute thyroiditis:
relationship with concomitant changes in serum T4-binding globulin concentration.
J Endocrinol Invest.
1993;
16
213-218
- 18
Okamoto H, Yamamura M, Morita Y, Harada S, Makino H, Ota Z.
The synovial expression and serum levels of interleukin-6, interleukin-11, leukemia
inhibitory factor, and oncostatin M in rheumatoid arthritis.
Arthritis Rheum.
1997;
40
1096-1105
- 19
Herrmann W, Ecker D, Quast S, Klieden M, Rose S, Marzi I.
Comparison of procalcitonin, sCD14 and interleukin-6 values in septic patients.
Clin Chem Lab Med.
2000;
38
41-46
- 20
Pichler R, Berg J, Crespillo C, Hatzl-Griesenhofer M, Huber H, Maschek W.
Hipertiroidismo de Graves y modulación por citoquinas proinflamatorias: el papel de
TNF-R e IL-6 en la fase aguda.
Endocrinología.
2001;
48 (supl. 2)
53 (abstract)
- 21
Fraunberger P, Pfeiffer M, Cremer P, Holler E, Nagel D, Dehart I, Thein M, Walli A K,
Seidel D.
Validation of an automated enzyme immunoassay for Interleukin-6 for routine clinical
use.
Clin Chem Lab Med.
1998;
36
797-801
- 22
Heilig B, Wermann M, Gallati H, Brockhaus M, Berke B, Egen O, Pezzutto A, Hunstein W.
Elevated TNF receptor plasma concentrations in patients with rheumatoid arthritis.
Clin Investig.
1992;
70
22-27
- 23
Mariotti S, Caturegli P, Barbesino G, Marino M, Del Prete G F, Chiovato L, Tonacchera M,
de Carli M, Pinchera A.
Thyroid function and thyroid autoimmunity independently modulate serum concentration
of soluble interleukin 2 (IL-2) receptor (sIL-2R) in thyroid diseases.
Clin Endocrinol.
1992;
37
415-422
- 24
Smallridge R C, Tsokos G C, Burman K D, Porter L, Cranston T, Sfikakis P P, Solomon B L.
Soluble interleukin-2 receptor is a thyroid hormone-dependent early-response marker
in the treatment of thyrotoxicosis.
Clin Diagn Lab Immunol.
1997;
4
583-586
- 25
Díez J J, 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.
2002;
57
515-521
- 26
Komorowski J, Jankiewicz J, Robak T, Blasinska-Morawiec M, Stepien H.
Cytokines serum levels as the markers of thyroid activation in Graves' disease.
Immunol Lett.
1998;
60
143-148
- 27
Wakelkamp I MMJ, Gerding M N, van der Meer J WC, Prummel M F, Wiersinga W M.
Both Th1 and Th2-derived cytokines in serum are elevated in Graves' ophthalmopathy.
Clin Exp Immunol.
2000;
121
453-457
- 28
Feldt-Rasmussen U, Schleusener H, Carayon P.
Meta-analysis evaluation of the impact of thyrotropin receptor antibodies on long
term remission after medical therapy of Graves' disease.
J Clin Endocrinol Metab.
1994;
78
98-102
- 29
Schleusener H, Schwander J, Fischer C, Holle R, Holl G, Badenhoop K, Hensen J, Finke R,
Bogner U, Mayr W R. et al .
Prospective multicenter study on the prediction of relapse after antithyroid drug
treatment in patients with Graves' disease.
Acta Endocrinol.
1989;
120
689-701
- 30
Wallaschofski H, Miehle K, Mayer A, Tuschy U, Hentschel B, Paschke R.
Prediction of Remission or Relapse for Graves' Hyperthyroidism by the Combined Determination
of Stimulating, Blocking and Binding TSH-Receptor Antibodies after the Withdrawal
of Antithyroid Drug Treatment.
Horm Metab Res.
2002;
34
383-388
- 31
Nygaard B, Jarlov A E, Kristensen L O, Faber J.
Serum levels of the cytokines IL-1beta, IL-6 and ICAM-1 after 131I-treatment of Graves'
disease and nodular goiter.
Horm Metab Res.
2000;
32
283-287
- 32
Heufelder A E.
Pathogenesis of Graves' ophthalmopathy: recent controversies and progress.
Eur J Endocrinol.
1995;
132
532-541
- 33
Hiromatsu Y, Yang D, Bednarczuk T, Miyake I, Nonaka K, Inoue Y.
Cytokine profiles in eye muscle tissue and orbital fat tissue from patients with thyroid-associated
ophthalmopathy.
J Clin Endocrinol Metab.
2000;
85
1194-1199
- 34
Mysliwiec J, Kretowski A, Topolska J, Siewko K, Jakubczyk D, Szelachowska M, Mikita A,
Kinalska I.
Serum Th1 and Th2 profile cytokine level changes in patients with Graves' ophthalmopathy
treated with corticosteroids.
Horm Metab Res.
2001;
33
739-743
R. Pichler, M. D., Ph. D.
Institute of Nuclear Medicine and Endocrinology, AKH Linz
Krankenhausstr. 9 · 4020 Linz · Austria
Telefon: +43(70)7806-6144
Fax: +43(70)7806-6165
eMail: Robert.Pichler@akh.linz.at
