title: Leuprolide Acetate Inhibits Spinal Cord Inflammatory Response in Experimental Autoimmune Encephalomyelitis by Suppressing NF-κB Activation.
abstract: OBJECTIVE
  Recent findings have shown that gonadotropin-releasing hormone (GnRH) administration in an animal model of multiple sclerosis (experimental autoimmune encephalomyelitis, EAE) improves clinical signs of locomotion. The present study was designed to determine whether the administration of the synthetic analog of GnRH, leuprolide acetate (LA) - besides its effects on clinical signs of locomotion - also has an effect on the activation/expression levels of molecular markers of EAE, namely transcription nuclear factor (NF)-κB and the proinflammatory cytokines IL-1β, IL-17A, IL-23 and TNF-α.
  
  
  METHODS
  EAE spinal cords were collected from control and LA-administered rats. Lumbar sections were processed at four different time points during the course of the disease to analyze NF-κB activation by chemiluminescent Western blot, and during the EAE recovery phase to evaluate proinflammatory cytokine levels by quantitative real-time PCR.
  
  
  RESULTS
  It was found that LA administration to EAE rats promoted a significant reduction of NF-κB activation during the course of the disease and also decreased the mRNA expression levels of the proinflammatory cytokines IL-1β, IL-17A and TNF-α in the EAE recovery phase; both effects are consistent with the decrease in the severity of clinical signs of locomotion induced by the treatment.
  
  
  CONCLUSIONS
  LA causes a reduction in the severity of locomotor activity, as well as in the activation of NF-κB and the number of proinflammatory markers in rats with EAE. These results suggest the use of this agonist as a potential therapeutic approach for multiple sclerosis.
authors.affiliation: Laboratory of Neurophysiology, Department of Physiology and Pharmacology, Centro de Ciencias Bx00E1;sicas, Universidad Autx00F3;noma de Aguascalientes, Aguascalientes, Mexico.
authors.forename: Irene
authors.initials: I
authors.lastname: Guzmán-Soto
authors.forename: Eva
authors.initials: E
authors.lastname: Salinas
authors.forename: J Luis
authors.initials: JL
authors.lastname: Quintanar
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000150:complications* / Q000276:immunology; D005260:Female; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D016729:Leuprolide / Q000627:therapeutic use*; D009187:Myelitis / Q000188:drug therapy* / Q000209:etiology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010052:Ovariectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016729:Leuprolide