This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hiromatsu, Y. Articles by Inoue, Y. Search for Related Content PubMed PubMed Citation Articles by Hiromatsu, Y. Articles by Inoue, Y.

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

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 (IFN), tumor necrosis factor (TNF), interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-10, CD4, CD8, and glyceraldehyde-3-phosphate dehydrogenase. IFN, TNF, 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, 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 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.

This article has been cited by other articles:

				M. Rotondi, L. Chiovato, S. Romagnani, M. Serio, and P. Romagnani Role of Chemokines in Endocrine Autoimmune Diseases Endocr. Rev., August 1, 2007; 28(5): 492 - 520. [Abstract] [Full Text] [PDF]

				B. Chen, S. Tsui, W. E. Boeglin, R. S. Douglas, A. R. Brash, and T. J. Smith Interleukin-4 Induces 15-Lipoxygenase-1 Expression in Human Orbital Fibroblasts from Patients with Graves Disease: EVIDENCE FOR ANATOMIC SITE-SELECTIVE ACTIONS OF Th2 CYTOKINES J. Biol. Chem., July 7, 2006; 281(27): 18296 - 18306. [Abstract] [Full Text] [PDF]

				A. Antonelli, M. Rotondi, S. M. Ferrari, P. Fallahi, P. Romagnani, S. S. Franceschini, M. Serio, and E. Ferrannini Interferon-{gamma}-Inducible {alpha}-Chemokine CXCL10 Involvement in Graves' Ophthalmopathy: Modulation by Peroxisome Proliferator-Activated Receptor-{gamma} Agonists J. Clin. Endocrinol. Metab., February 1, 2006; 91(2): 614 - 620. [Abstract] [Full Text] [PDF]

				R. Han and T. J. Smith T Helper Type 1 and Type 2 Cytokines Exert Divergent Influence on the Induction of Prostaglandin E2 and Hyaluronan Synthesis by Interleukin-1{beta} in Orbital Fibroblasts: Implications for the Pathogenesis of Thyroid-Associated Ophthalmopathy Endocrinology, January 1, 2006; 147(1): 13 - 19. [Abstract] [Full Text] [PDF]

				B. Chen, S. Tsui, and T. J. Smith IL-1{beta} Induces IL-6 Expression in Human Orbital Fibroblasts: Identification of an Anatomic-Site Specific Phenotypic Attribute Relevant to Thyroid-Associated Ophthalmopathy J. Immunol., July 15, 2005; 175(2): 1310 - 1319. [Abstract] [Full Text] [PDF]

				R. Han and T. J. Smith Induction by IL-1{beta} of Tissue Inhibitor of Metalloproteinase-1 in Human Orbital Fibroblasts: Modulation of Gene Promoter Activity by IL-4 and IFN-{gamma} J. Immunol., March 1, 2005; 174(5): 3072 - 3079. [Abstract] [Full Text] [PDF]

				S. Kumar, M. J. Coenen, P. E. Scherer, and R. S. Bahn Evidence for Enhanced Adipogenesis in the Orbits of Patients with Graves' Ophthalmopathy J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 930 - 935. [Abstract] [Full Text] [PDF]

				B. S. Prabhakar, R. S. Bahn, and T. J. Smith Current Perspective on the Pathogenesis of Graves' Disease and Ophthalmopathy Endocr. Rev., December 1, 2003; 24(6): 802 - 835. [Abstract] [Full Text] [PDF]

				S. Kumar and R. S. Bahn Relative Overexpression of Macrophage-Derived Cytokines in Orbital Adipose Tissue from Patients with Graves' Ophthalmopathy J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4246 - 4250. [Abstract] [Full Text] [PDF]

				R. S. Bahn Pathophysiology of Graves' Ophthalmopathy: The Cycle of Disease J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 1939 - 1946. [Full Text] [PDF]

				W. M. Wiersinga and M. F. Prummel Pathogenesis of Graves' Ophthalmopathy--Current Understanding J. Clin. Endocrinol. Metab., February 1, 2001; 86(2): 501 - 503. [Full Text]