title: Elevated macrophage migration inhibitory factor and decreased transforming growth factor-beta levels in major depression--no influence of celecoxib treatment.
abstract: OBJECTIVE
  The involvement of an immune process in the pathophysiology of major depression disorder (MDD) was substantiated by studies demonstrating elevated levels of proinflammatory cytokines and prostaglandin E(2) (PGE(2)). Cyclooxygenase-2 (COX-2) inhibitors lead to a reduced production of PGE(2) and have been shown to improve depressive symptoms. We investigated the three immune parameters macrophage migration inhibitory factor (MIF), transforming growth factor-β (TGF-β) and soluble CD14 (sCD14) in a randomized, placebo-controlled trial of the COX-2 inhibitor celecoxib as add-on therapy in patients with MDD treated with reboxetine.
  
  
  METHODS
  Thirty-two patients with depression and 20 healthy controls participated in the study. The patients were treated with reboxetine and celecoxib or placebo. Immune parameters were measured from serum at baseline, after three and five weeks using ELISA.
  
  
  RESULTS
  Celecoxib as add-on strategy resulted in a significant reduction of Hamilton Depression Scale scores compared to placebo. Depressed patients showed significantly elevated MIF (p < 0.001) and reduced TGF-β (p = 0.006) concentrations at baseline. There was no difference in sCD14-concentrations. There was no difference between the placebo and the celecoxib group and no change over time.
  
  
  CONCLUSIONS
  Limitations of the study are the relatively small sample size and lack of functional assessment of HPA axis in parallel.
  
  
  CONCLUSIONS
  MIF is a promising new candidate in the neuro-immune interplay that may link depressive symptoms, altered immune state and HPA-axis dysregulation. Reduced levels of TGF-β replicate previous findings and support the importance of this regulatory cytokine in major depressive disorder.
authors.affiliation: Psychiatric Clinic of University Munich, Nussbaumstrasse 7, 80336 Munich, Germany. Richard.musil@med.uni-muenchen.de
authors.forename: R
authors.initials: R
authors.lastname: Musil
authors.forename: M J
authors.initials: MJ
authors.lastname: Schwarz
authors.forename: M
authors.initials: M
authors.lastname: Riedel
authors.forename: S
authors.initials: S
authors.lastname: Dehning
authors.forename: A
authors.initials: A
authors.lastname: Cerovecki
authors.forename: I
authors.initials: I
authors.lastname: Spellmann
authors.forename: V
authors.initials: V
authors.lastname: Arolt
authors.forename: N
authors.initials: N
authors.lastname: Müller
mesh_terms: D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use; D000068579:Celecoxib; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003863:Depression; D003866:Depressive Disorder / Q000188:drug therapy; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009025:Morpholines / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D011581:Psychological Tests; D011720:Pyrazoles / Q000627:therapeutic use*; D000077593:Reboxetine; D013449:Sulfonamides / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents; D052246:Cyclooxygenase 2 Inhibitors; D008263:Macrophage Migration-Inhibitory Factors; D009025:Morpholines; D011720:Pyrazoles; D013449:Sulfonamides; D016212:Transforming Growth Factor beta; D000077593:Reboxetine; D051546:Cyclooxygenase 2; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human; C022346:phenylpyruvate tautomerase; D000068579:Celecoxib