title: Acute effects of low-dose interferon-alpha on serum cortisol and plasma interleukin-6.
abstract: Major depression is associated with both hypothalamic-pituitary-adrenal (HPA) axis overactivity and immune system activation. Depression is a common occurrence following interferon (IFN)-a treatment. While IFN-alpha is known to stimulate the HPA axis, little is known about the effects of exogenous IFN-a in humans on the proinflammatory cytokine interleukin (IL)-6, a marker of immune system activation. This study examined the acute effects of IFN-alpha on cortisol and IL-6 release, and the time course of any changes in these variables. Serum cortisol and plasma IL-6 were assessed in healthy volunteers over an 8-h period following 3 million units subcutaneous IFN-alpha or placebo using a double-blind, placebo-controlled crossover design. IFN-alpha resulted in a significant increase in both cortisol and IL-6. Regular sampling over 8 h did not delineate any sequential effect of the rise in these variables over time. We conclude that IFN-alpha acutely stimulates both the HPA axis and proinflammatory cytokine release. The hypothesis that the effect of IFN-alpha on the HPA axis is indirect and mediated by IL-6 was not supported by this study. Our findings are nonetheless of relevance to the aetiology of depression following IFN-alpha.
authors.affiliation: Department of Psychiatry, Royal College of Surgeons, Beaumont Hospital, Dublin, Eire, Ireland. eucass@hotmail.com
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Cassidy
authors.forename: Diarmuid
authors.initials: D
authors.lastname: Manning
authors.forename: Sinead
authors.initials: S
authors.lastname: Byrne
authors.forename: Emer
authors.initials: E
authors.lastname: Bolger
authors.forename: Frank
authors.initials: F
authors.lastname: Murray
authors.forename: Neda
authors.initials: N
authors.lastname: Sharifi
authors.forename: Eleanor
authors.initials: E
authors.lastname: Wallace
authors.forename: Mary
authors.initials: M
authors.lastname: Keogan
authors.forename: Veronica
authors.initials: V
authors.lastname: O'Keane
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D003865:Major Depressive Disorder / Q000139:chemically induced* / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D011994:Recombinant Proteins
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D015850:Interleukin-6; D011994:Recombinant Proteins; D006854:Hydrocortisone