The effect of types I and III interferons on adrenocortical cells and its possible implications for autoimmune A ddison's disease

Summary Autoimmune A ddison'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 ‐ H 295 R 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 .