Serum IL-18 Levels are not Increased in Patients with Untreated Graves' Ophthalmopathy

Abstract

Objective: Cytokines play an important role in autoimmune thyroid diseases, and serum levels may reflect the activity of the immune process. This is particularly interesting in Graves’ ophthalmopathy, where a reliable serum activity marker is warranted. Interleukin-18 (IL-18) is a potent Th1 cytokine, known to induce interferon (IFN)-gamma and the aim of this study was to evaluate serum IL-18 levels in Graves’ ophthalmopathy. Methods: Serum IL-18 was measured by ELISA in 52 patients with untreated Graves’ ophthalmopathy (who all had been rendered euthyroid with antithyroid drugs), 52 healthy controls matched for sex, age, and smoking habits, and 15 euthyroid patients who had been treated for Graves’ hyperthyroidism and ophthalmopathy in the past. Results: Serum IL-18 (median values in pg/ml with range) levels did not differ between the untreated Graves’ ophthalmopathy patients - 226 (61 - 704) pg/ml, matched healthy controls - 194 (17 - 802) pg/ml, and Graves’ ophthalmopathy patients treated in the past - 146 (0 - 608) pg/ml. No correlation was observed between serum IL-18 levels and thyroid function or antithyroid antibodies. There was no correlation between serum IL-18 levels and smoking habits. Conclusion: We conclude that Graves’ ophthalmopathy does not affect serum IL-18.

Key words

Graves’ ophthalmopathy - Autoimmune thyroid diseases - Serum IL-18 - ELISA

References

• 1 McInnes I B, Gracie J A, Leung B P, Wie X Q, Liew F Y. Interleukin 18: a pleiotropic participant in chronic inflammation.  Immunology Today. 2000;  21 312-315
• 2 Lebel-Binay S, Berger A, Zinzindohoue F, Cugnenc P, Thiounn N, Fridman W H, Pages F. Interleukin-18: biological properties and clinical implications.  European Cytokine Network. 2000;  11 15-26
• 3 Gracie J A, Forsey R J, Chan W L, Gilmour A, Leung B P, Greer M R, Kennedy K, Carter R, Wie X Q, Xu D, Field M, Foulis A, Liew F Y, McInnes I B. A proinflammatory role for IL-18 in rheumatoid arthritis.  J Clin Invest. 1999;  104 1393-1401
• 4 Tanaka K F, Shintani F, Fujii Y, Yagi G, Asai M. Serum interleukin-18 levels are elevated in schizophrenia.  Psychiatry Res. 2000;  96 75-80
• 5 Urushihara N, Iwagaki H, Yagi T, Kohka H, Kobashi K, Morimoto Y, Yoshino T, Tanimoto T, Kurimoto M, Tanaka N. Elevation of serum interleukin-18 levels and activation of Kupffer cells in biliary atresia.  J Pediatr Surg. 2000;  35 446-449
• 6 Losy J, Niezgoda A. IL-18 in patients with multiple sclerosis.  Acta Neurol Scand. 2001;  104 171-173
• 7 Miyauchi S, Matsuura B, Onji M. Increased levels of serum interleukin-18 in Graves’ disease.  Thyroid. 2000;  10 815-819
• 8 Prummel M F, Wiersinga W M, Van der Gaag R, Mourits M P, Koornneef L. Soluble IL-2 receptor levels in patients with Graves’ ophthalmopathy.  Clinical & Experimental Immunology. 1992;  88 405-409
• 9 Salvi M, Girasole G, Pedrazzoni M, Passeri M, Giuliani N, Minelli R, Braverman L E, Roti E. Increased serum concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor in patients with Graves’ disease.  Journal of Clinical Endocrinology & Metabolism. 1996;  81 2976-2979
• 10 Hofbauer L C, Muhlberg T, Konig A, Heufelder G, Schworm H D, Heufelder A E. Soluble Interleukin-1 receptor antagonist serum levels in smokers and nonsmokers with Graves ophthalmopathy undergoing orbital radiotherapy.  Journal of Clinical Endocrinology & Metabolism. 1997;  82 2244-2247
• 11 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
• 12 Wakelkamp I MMJ, Gerding M N, van der Meer J W, Prummel M F, Wiersinga W M. Both Th1- and Th2-derived cytokines in serum are elevated in Graves’ ophthalmopathy.  Clinical & Experimental Immunology. 2000;  121 453-457
• 13 Prummel M F, Mourits M P, Berghout A, Krenning E P, van der Gaag R, Koornneef L, Wiersinga W M. Prednisone and cyclosporine in the treatment of severe Graves’ ophthalmopathy.  New England Journal of Medicine. 1989;  321 1353-1359
• 14 Mourits M P, Koornneef L, Wiersinga W M, Prummel M F, Berghout A, van der Gaag R. Clinical criteria for the assessment of disease activity in Graves’ ophthalmopathy: a novel approach.  British Journal of Ophthalmology. 1989;  73 639-644
• 15 Bartalena L, Pinchera A, Marcocci C. Management of Graves’ ophthalmopathy: reality and perspectives.  Endocrine Reviews. 2000;  21 168-199
• 16 Wakelkamp I MMJ, Bakker O, Baldeschi L, Wiersinga W M, Prummel M F. TSH-R expression and cytokine profile in orbital tissue of active vs. inactive Graves’ ophthalmopathy patients.  Clin Endocrinol (Oxf). 2003;  58 280-287
• 17 Wakelkamp I MMJ, Gerding M N, van der Meer J WC, Prummel M F, Wiersinga W M. Smoking and disease severity are independent determinants of serum adhesion molecule levels in Graves’ ophthalmopathy.  Clinical & Experimental Immunology. 2002;  127 316-320
• 18 Prummel M F, Wiersinga W M. Smoking and risk of Graves’ disease.  JAMA. 1993;  269 479-482
• 19 Tellez M, Cooper J, Edmonds C. Graves’ ophthalmopathy in relation to cigarette smoking and ethnic origin.  Clinical Endocrinology. 1992;  36 291-294
• 20 Shine B, Fells P, Edwards O M, Weetman A P. Association between Graves’ ophthalmopathy and smoking.  Lancet. 1990;  335 1261-1263