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The Journal of Clinical Endocrinology & Metabolism Vol. 85, No. 3 1194-1199
Copyright © 2000 by The Endocrine Society


Original Studies

Cytokine Profiles in Eye Muscle Tissue and Orbital Fat Tissue from Patients with Thyroid-Associated Ophthalmopathy1

Yuji Hiromatsu, Dame Yang, Tomasz Bednarczuk, Ikuyo Miyake, Kyohei Nonaka and Yoichi Inoue

Division of Endocrinology and Metabolism, Department of Medicine (Y.H., D.Y., T.B., I.M., K.N.), Fukuoka 830-0011, Japan; Eye Division, Olympia Medical Clinic (Y.I.), Tokyo 150-0001, Japan; and Department of Endocrinology, Polish Academy of Science (T.B.), Warsaw 02-097, Poland

Address correspondence and requests for reprints to: Yuji Hiromatsu, M.D., Division of Endocrinology and Metabolism, Department of Medicine, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011 Japan. E-mail: yuji{at}med.kurume-u.ac.jp

Eye muscle (EM) and retroorbital fat tissue are two major sites of involvement in thyroid-associated ophthalmopathy (TAO). Lymphocytic infiltration in these tissues is a prominent histological feature of TAO. We have investigated the cytokine gene profiles in EM and orbital fat (OF) tissues from patients with TAO. Total RNA was isolated from EM tissue of 14 patients and from OF tissues of 29 patients with TAO. Cytokine gene expression was assessed by RT-PCR using paired primers for interferon {gamma} (IFN{gamma}), tumor necrosis factor {alpha} (TNF{alpha}), interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-10, CD4, CD8, and glyceraldehyde-3-phosphate dehydrogenase. IFN{gamma}, TNF{alpha}, IL-1ß, and IL-6 messenger RNA (mRNA) were mainly detected in EM tissue, whereas IL-4 and IL-10 mRNA were detected in only one patient. On the other hand, in OF tissue, IL-4 and IL-10 mRNA were detected in 24% and 38% of the patients, respectively, and IFN{gamma}, IL-1ß, and IL-6 mRNA were less often detected compared with EM tissue. The enlargement of EM tissue as assessed by computed tomography correlated significantly with TNF{alpha} mRNA expression in EM tissue. The orbital volume was positively correlated with IL-6 mRNA expression and negatively correlated with IL-4 mRNA and IL-10 mRNA expression in OF tissue. These results suggest that T helper (Th) 1-like cytokines predominate in EM tissue in most patients and that the predominant cytokine profile in OF tissue varies from patient to patient. Both Th1-like and Th2-like immune responses may play roles in the development of two components of ophthalmopathy.




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