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Submitted on June 8, 2004
Accepted on January 3, 2005
inducible chemokine IP-10/CXCL10 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", Chair of Endocrinology, Second University of Naples (M.R., A.D., A. Be.) Department of Internal Medicine (A.F., S.L., F.S.) University of Perugia, and Department of Clinical Pathophysiology, Endocrinology Unit, (P.F., P.R., A. Bu., E.L., C.C., M.M., M.S.) University of Florence, Italy
* To whom correspondence should be addressed. 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, 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 patient with clinically evident autoimmune AD, 20 patients with autoimmune subclinical AD, 9 patients with nonautoimmune AD and in 48 healthy volunteers. Clinically evident and subclinical AD, but not non autoimmune AD patients, showed a significant increase in serum CXCL10 levels when compared with healthy subjects: 119.9 pg/ml (39.8-427.6) and 124.0 pg/ml (37.0-384.7) vs. 75.6 pg/ml (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 to AD, suggesting a specific influence of the adrenal autoimmune process in determining raised 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.
CXCL10 role in adrenal gland was further evaluated in vitro in human Zona Fasciculata cells (hZFC). CXCL10, although not basally detected in cultured hZFC, was strongly induced by IFN-
and synergistically increased by TNF-
addition. Hydrocortisone or ACTH alone had no effect on CXCL10 secretion in hZFC, but they both significantly inhibited cytokines-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.
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