title: Chronobiology and the treatment of rheumatoid arthritis.
abstract: OBJECTIVE
  As circadian rhythms and biological signaling occur in a complex network with cyclical 24-h period interactions (chronobiology) between the central and the autonomic nervous systems, the endocrine glands and the immune system, this review will explore the involvement of this emerging network in the disease pathophysiology and management.
  
  
  RESULTS
  Recent advances regarding nocturnal hormones such as melatonin and prolactin that activate the nighttime immune response, and the successive rise of cortisol that dowregulates the ongoing immune reactivity very early in the morning, will be discussed within the circadian neuroendocrine immune network. In addition, the role of sleep and the daily distribution of body energy, which are important factors for the homoeostatic regulation of circadian physiological/pathological processes of the immune network will be reviewed.In chronic immune/inflammatory conditions such as rheumatoid arthritis (RA), stiffness and functional disability are evident in the early morning hours as under the chronic stress of the disease the nighttime adrenal cortisol production becomes insufficient to inhibit ongoing nocturnal immune/inflammatory activity.
  
  
  CONCLUSIONS
  Currently, the most advanced approach to optimizing the risk-benefit ratio for long-term glucocorticoid treatment in RA seems to be low-dose chronotherapy with modified nighttime release prednisone (release at 3 a.m.). A similar chronotherapeutical approach could also be effective with disease-modifying antirheumatic drugs such as methotrexate.
authors.affiliation: Research Laboratories and Academic Unit of Clinical Rheumatology, Department of Internal Medicine, University of Genova, Genova, Italy. mcutolo@unige.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Cutolo
mesh_terms: D018501:Antirheumatic Agents / Q000008:administration & dosage; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D002940:Circadian Rhythm / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis; D055870:Drug Chronotherapy; D004734:Energy Metabolism / Q000502:physiology; D005938:Glucocorticoids / Q000008:administration & dosage; D006801:Humans; D012890:Sleep / Q000502:physiology
chemical_list: D018501:Antirheumatic Agents; D016207:Cytokines; D005938:Glucocorticoids