title: Apparent Hypothalamic-Pituitary-Adrenal Axis Suppression via Reduction of Interleukin-6 by Glucocorticoid Therapy in Systemic Autoimmune Diseases.
abstract: BACKGROUND
  Suppression of the hypothalamic-pituitary-adrenal (HPA) axis is a serious complication of systemic glucocorticoid therapy.
  
  
  OBJECTIVE
  To clarify the influence of proinflammatory cytokines on the HPA axis after onset of glucocorticoid therapy in patients with systemic autoimmune diseases.
  
  
  METHODS
  Forty-eight glucocorticoid-naïve patients with systemic autoimmune diseases (28 women) who were starting prednisolone therapy according to our standard regimens were prospectively observed. Patients were classified into high-dose and low-dose groups depending on the dose of prednisolone administered as indicated for their diseases. Plasma adrenocorticotropic hormone (ACTH) and serum cortisol levels were measured by electrochemiluminescence immunoassay. The corticotropin-releasing hormone (CRH) test was performed at baseline and second and forth weeks after starting glucocorticoid therapy. The increased levels of ACTH (ΔACTH) and cortisol (Δcortisol) were investigated. Serum levels of 10 proinflammatory cytokines were measured simultaneously by a multi-spot assay system.
  
  
  RESULTS
  In the high-dose group, both basal and stimulated levels of ACTH and cortisol were significantly decreased by glucocorticoid therapy. In the low-dose group, basal ACTH and cortisol levels were also significantly decreased by glucocorticoid therapy, but ΔACTH and Δcortisol were unchanged. Among 10 cytokines, only interleukin (IL)-6 was significantly decreased by glucocorticoid therapy in both groups and was more closely correlated with cortisol than ACTH. Basal cortisol level was positively correlated with serum IL-6 level in all patients before glucocorticoid therapy.
  
  
  CONCLUSIONS
  In patients with systemic autoimmune diseases, apparent suppression of cortisol during glucocorticoid therapy may be partly mediated by reduced production of IL-6.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Faculty of Medicine, Toho University, Ota-ku, Tokyo, Japan.
authors.forename: Natsuki
authors.initials: N
authors.lastname: Fujio
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Faculty of Medicine, Toho University, Ota-ku, Tokyo, Japan.
authors.forename: Shotaro
authors.initials: S
authors.lastname: Masuoka
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Faculty of Medicine, Toho University, Ota-ku, Tokyo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Shikano
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Faculty of Medicine, Toho University, Ota-ku, Tokyo, Japan.
authors.forename: Natsuko
authors.initials: N
authors.lastname: Kusunoki
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Faculty of Medicine, Toho University, Ota-ku, Tokyo, Japan.
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nanki
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, School of Medicine, Faculty of Medicine, Toho University, Ota-ku, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kawai
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000368:Aged; D001327:Autoimmune Diseases / Q000188:drug therapy*; D016207:Cytokines / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System; D000093242:Interleukin-6 Inhibitors
chemical_list: D000324:Adrenocorticotropic Hormone; D016207:Cytokines; D005938:Glucocorticoids; D006854:Hydrocortisone; D018836:Inflammation Mediators; D015850:Interleukin-6; D000093242:Interleukin-6 Inhibitors