title: Mechanistic insights into corticosteroids in multiple sclerosis: war horse or chameleon?.
abstract: OBJECTIVE
  Relapse management is a crucial component of multiple sclerosis (MS) care. High-dose corticosteroids (CSs) are used to dampen inflammation, which is thought to hasten the recovery of MS relapse. A diversity of mechanisms drive the heterogeneous clinical response to exogenous CSs in patients with MS. Preclinical research is beginning to provide important insights into how CSs work, both in terms of intended and unintended effects. In this article we discuss cellular, systemic, and clinical characteristics that might contribute to intended and unintended CS effects when utilizing supraphysiological doses in clinical practice. The goal of this article is to consider recent insights about CS mechanisms of action in the context of MS.
  
  
  METHODS
  We reviewed relevant preclinical and clinical studies on the desirable and undesirable effects of high-dose corticosteroids used in MS care.
  
  
  RESULTS
  Preclinical studies reviewed suggest that corticosteroids may act in unpredictable ways in the context of autoimmune conditions. The precise timing, dosage, duration, cellular exposure, and background CS milieu likely contribute to their clinical heterogeneity.
  
  
  CONCLUSIONS
  It is difficult to predict when patients will respond favorably to CSs, both in terms of therapeutic response and tolerability profile. There are specific cellular, systemic, and clinical characteristics that might merit further consideration when utilizing CSs in clinical practice, and these should be explored in a translational setting.
authors.affiliation: Corinne Goldsmith Dickinson Center for MS, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Krieger
authors.affiliation: Department of Neurosurgery, The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, California, USA.
authors.forename: Shawn F
authors.initials: SF
authors.lastname: Sorrells
authors.affiliation: Questcor Pharmaceuticals, Hayward, California, USA.
authors.forename: Molly
authors.initials: M
authors.lastname: Nickerson
authors.affiliation: College of Nursing and College of Medicine (Department of Psychiatry), University of Arizona, Tucson, Arizona, USA. Electronic address: twwpace@email.arizona.edu.
authors.forename: Thaddeus W W
authors.initials: TW
authors.lastname: Pace
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003865:Major Depressive Disorder / Q000150:complications / Q000523:psychology; D018450:Disease Progression; D006801:Humans; D009103:Multiple Sclerosis / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents
keywords: Corticosteroids; Exacerbations; Glucocorticoids; Multiple sclerosis; Relapses