title: Effect of novel therapeutic glucocorticoids on circadian rhythms of hormones and cytokines in rheumatoid arthritis.
abstract: The morning stiffness and pain of rheumatoid arthritis (RA) is accompanied by a rise in serum interleukin-6 (IL-6) from 2 am to 7 am. Using a formulation that releases prednisone at 2 am (after ingestion at 10 pm), we studied the circadian dynamics of serum IL-6, other cytokines, and cortisol in 9 patients before and after 2 weeks, therapy. Significant improvements occurred in morning stiffness, pain, disease activity, and the acute-phase response. Only IL-6 showed measurable cytokine circadian variation, its high pretreatment peak was abolished, and changes in IL-6 correlated with the changes in morning stiffness. Following treatment, afternoon and evening serum cortisol was reduced, but in the early morning cortisol peak concentration increased. Thus the severity of morning symptoms is related to nocturnal serum IL-6 concentration. The specific timing of the medication, linked to the interaction between IL-6 and the hypothalamic-pituitary-adrenal (HPA) axis, may correct a postulated deficiency in HPA control in RA.
authors.affiliation: University of Bristol Academic Rheumatology Unit, Bristol Royal Infirmary, Bristol, UK. John.Kirwan@Bristol.ac.uk
authors.forename: John R
authors.initials: JR
authors.lastname: Kirwan
authors.forename: Lynsey
authors.initials: L
authors.lastname: Clarke
authors.forename: Linda P
authors.initials: LP
authors.lastname: Hunt
authors.forename: Mark G
authors.initials: MG
authors.lastname: Perry
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Straub
authors.forename: David S
authors.initials: DS
authors.lastname: Jessop
mesh_terms: D000893:Anti-Inflammatory Agents / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000097:blood*; D002940:Circadian Rhythm / Q000502:physiology*; D016207:Cytokines / Q000097:blood*; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use*; D006728:Hormones / Q000097:blood*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D011241:Prednisone / Q000378:metabolism; D013607:Tablets
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D006728:Hormones; D015850:Interleukin-6; D013607:Tablets; D011241:Prednisone; D006854:Hydrocortisone