title: The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune Addison's disease.
abstract: Autoimmune Addison's disease (AAD) is caused by selective destruction of the hormone-producing cells of the adrenal cortex. As yet, little is known about the potential role played by environmental factors in this process. Type I and/or type III interferons (IFNs) are signature responses to virus infections, and have also been implicated in the pathogenesis of autoimmune endocrine disorders such as type 1 diabetes and autoimmune thyroiditis. Transient development of AAD and exacerbation of established or subclinical disease, as well as the induction of autoantibodies associated with AAD, have been reported following therapeutic administration of type I IFNs. We therefore hypothesize that exposure to such IFNs could render the adrenal cortex susceptible to autoimmune attack in genetically predisposed individuals. In this study, we investigated possible immunopathological effects of type I and type III IFNs on adrenocortical cells in relation to AAD. Both types I and III IFNs exerted significant cytotoxicity on NCI-H295R adrenocortical carcinoma cells and potentiated IFN-γ- and polyinosine-polycytidylic acid [poly (I : C)]-induced chemokine secretion. Furthermore, we observed increased expression of human leucocyte antigen (HLA) class I molecules and up-regulation of 21-hydroxylase, the primary antigenic target in AAD. We propose that these combined effects could serve to initiate or aggravate an ongoing autoimmune response against the adrenal cortex in AAD.
authors.affiliation: Section for Endocrinology, Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: A
authors.initials: A
authors.lastname: Hellesen
authors.forename: K
authors.initials: K
authors.lastname: Edvardsen
authors.forename: L
authors.initials: L
authors.lastname: Breivik
authors.forename: E S
authors.initials: ES
authors.lastname: Husebye
authors.forename: E
authors.initials: E
authors.lastname: Bratland
mesh_terms: D000224:Addison Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000302:Adrenal Cortex / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D018925:Chemokines / Q000378:metabolism; D004357:Drug Synergism; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000187:drug effects; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D007372:Interferons / Q000378:metabolism* / Q000494:pharmacology / Q000633:toxicity; D011070:Poly I-C / Q000494:pharmacology; D017471:Receptors, Interferon / Q000235:genetics / Q000378:metabolism; D013255:Steroid 21-Hydroxylase / Q000235:genetics / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D051196:Toll-Like Receptor 3 / Q000378:metabolism
chemical_list: D018925:Chemokines; D015395:Histocompatibility Antigens Class I; D017471:Receptors, Interferon; D051196:Toll-Like Receptor 3; D007372:Interferons; D013255:Steroid 21-Hydroxylase; D011070:Poly I-C
keywords: 21-hydroxylase; Addison's disease; CXC chemokine ligand 10; interferon; polyinosine-polycytidylic acid