This Article Full Text Full Text (PDF) All Versions of this Article: 90/4/2357    most recent Author Manuscript (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 Rotondi, M. Articles by Serio, M. Search for Related Content PubMed PubMed Citation Articles by Rotondi, M. Articles by Serio, M. Related Collections Adrenal and Hypertension

Elevated Serum Interferon--Inducible Chemokine-10/CXC Chemokine Ligand-10 in Autoimmune Primary Adrenal Insufficiency and in Vitro Expression in Human Adrenal Cells Primary Cultures after Stimulation with Proinflammatory Cytokines

Department of Clinical and Experimental Medicine and Surgery F. Magrassi, A. Lanzara, Second University of Naples (M.R., A.D., A.Be.), 80131 Naples, Italy; Department of Internal Medicine, University of Perugia (A.F., S.L., F.S.), 06126 Perugia, Italy; and Department of Clinical Pathophysiology, Endocrinology Unit, University of Florence (P.F., P.R., A.Bu., E.L., C.C., M.M., M.S.), 50139 Firenze, Italy

Address all correspondence and requests for reprints to: Dr. Mario Serio, Department of Clinical Pathophysiology, Endocrinology Unit, University of Florence, V. le Pieraccini 6, 50139 Firenze, Italy. E-mail: m.serio{at}dfc.unifi.it.

Chemokines are a large family of cytokines involved in the pathogenesis of inflammatory and autoimmune diseases. Among CXC chemokines, CXC chemokine ligand 10 (CXCL10) has been identified to play an important role in several endocrinological autoimmune diseases, such as Hashimoto’s thyroiditis, Graves’ disease, and type 1 diabetes mellitus. Although the mechanisms leading to glandular autoimmune process may be at least in part shared by different endocrine organs, the role of CXCL10 in autoimmune adrenal insufficiency is unknown. The aim of this study was to evaluate the role of CXCL10 in Addison’s disease (AD). Serum CXCL10 levels were assayed in 64 patients with clinically evident autoimmune AD, 20 patients with autoimmune subclinical AD, nine patients with nonautoimmune AD, and 48 healthy volunteers. Clinically evident and subclinical AD, but not nonautoimmune AD patients, showed a significant increase in serum CXCL10 levels compared with healthy subjects: 119.9 pg/ml (range, 39.8–427.6) and 124.0 pg/ml (range, 37.0–384.7) vs. 75.6 pg/ml (range, 22.4–164.0; P < 0.001 for both groups). Comparable serum CXCL10 levels were found between patients with an isolated form of AD and patients with other autoimmune conditions associated with AD, suggesting a specific influence of the adrenal autoimmune process in determining elevated CXCL10 concentrations in such patients. No relationship was found between serum CXCL10 levels and anti-21-hydroxylase or adrenal cortex autoantibody titers or between CXCL10 levels and duration of disease. The role of CXCL10 in the adrenal gland was also evaluated in vitro in human zona fasciculata cells (hZFC). CXCL10, although not basally detected in cultured hZFC, was strongly induced by interferon- and synergistically increased by TNF- addition. Hydrocortisone or ACTH alone had no effect on CXCL10 secretion in hZFC, but they both significantly inhibited cytokine-induced CXCL10 secretion. Taken together, these data suggest a potential role of hZFC, through the production of CXCL10, in regulating the recruitment of specific subsets of activated lymphocytes in autoimmune AD.

This article has been cited by other articles:

				K. Kisand, M. Link, A. S. B. Wolff, A. Meager, L. Tserel, T. Org, A. Murumagi, R. Uibo, N. Willcox, K. Trebusak Podkrajsek, et al. Interferon autoantibodies associated with AIRE deficiency decrease the expression of IFN-stimulated genes Blood, October 1, 2008; 112(7): 2657 - 2666. [Abstract] [Full Text] [PDF]

				C Crescioli, L Cosmi, E Borgogni, V Santarlasci, S Gelmini, M Sottili, E Sarchielli, B Mazzinghi, M Francalanci, A Pezzatini, et al. Methimazole inhibits CXC chemokine ligand 10 secretion in human thyrocytes J. Endocrinol., October 1, 2007; 195(1): 145 - 155. [Abstract] [Full Text] [PDF]

				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]

				A. Antonelli, M. Rotondi, P. Fallahi, M. Grosso, G. Boni, S. M. Ferrari, P. Romagnani, M. Serio, G. Mariani, and E. Ferrannini Iodine-131 Given for Therapeutic Purposes Modulates Differently Interferon-{gamma}-Inducible {alpha}-Chemokine CXCL10 Serum Levels in Patients with Active Graves' Disease or Toxic Nodular Goiter J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1485 - 1490. [Abstract] [Full Text] [PDF]

				P. Romagnani, F. Annunziato, F. Liotta, E. Lazzeri, B. Mazzinghi, F. Frosali, L. Cosmi, L. Maggi, L. Lasagni, A. Scheffold, et al. CD14+CD34low Cells With Stem Cell Phenotypic and Functional Features Are the Major Source of Circulating Endothelial Progenitors Circ. Res., August 19, 2005; 97(4): 314 - 322. [Abstract] [Full Text] [PDF]