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Changes in expression of T-helper (Th) 1- and Th2-associated chemokine receptors on peripheral blood lymphocytes and plasma concentrations of their ligands, interferon-inducible protein-10 and thymus and activation-regulated chemokine, after antithyroid drug administration in hyperthyroid patients with Graves’ disease

Department of Internal Medicine, Koshigaya Hospital, Dokkyo Medical University, 2-1-50 Minami-Koshigaya, Koshigaya, Saitama 343-8555, Japan and ¹ Mitsubishi Kagaku Bio-Clinical Laboratories, Inc., Tokyo 174-8555, Japan

(Correspondence should be addressed to Y Aso; Email: yaso{at}dokkyomed.ac.jp)

Objective: Although Graves’ disease is considered an autoantibody-mediated, T-helper 2 (Th2)-dominant disease, Th1-dominance may prevail in its initial phase. We longitudinally investigated Th1/Th2 balance in untreated hyperthyroid patients with Graves’ disease after treatment of methimazole (MMI), an antithyroid drug.

Design: University clinic outpatients were studied prospectively.

Patients: Subjects included 23 untreated hyperthyroid patients with Graves’ disease and 17 age-matched control subjects.

Methods: Before and after treatment, we measured Th1- and Th2-associated chemokine receptors (CXCR)3 and CCR4, on peripheral blood lymphocytes using flow cytometry, as well as plasma concentrations of their ligands, interferon-inducible protein (IP)-10 and thymus and activation-regulated chemokine (TARC).

Results: The percentage of CXCR3-expressing cells among CD4⁺T lymphocytes and plasma IP-10 was significantly higher in hyperthyroid Graves’ disease patients than in controls. At 12 and 24 weeks after initiation of MMI, percentage of CXCR3-expressing CD4⁺T lymphocytes had decreased significantly, while the percentage of CCR4-expressing CD4⁺T lymphocytes had increased significantly at 24 weeks. The CXCR3/CCR4 ratio had decreased significantly at 24 weeks. Plasma concentrations of IP-10 had decreased significantly at 12 and 24 weeks. Plasma concentrations of TARC also had decreased significantly at 24 weeks.

Conclusions: In hyperthyroid patients with Graves’ disease in the active phase, Th1 cells rather than Th2 cells predominated among peripheral blood lymphocytes. After initiation of MMI, an ongoing transition from Th1 to Th2 dominance occurred.

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