title: Modulation of the contact hypersensitivity response by AE-941 (Neovastat), a novel antiangiogenic agent.
abstract: BACKGROUND
  AE-941 (Neovastat) is an angiogenesis inhibitor noted to have antiinflammatory properties.
  
  
  OBJECTIVE
  We tested Neovastat in a contact hypersensitivity (CHS) model to determine the mechanism of action of its antiinflammatory effects.
  
  
  METHODS
  Neovastat was orally administered (200 mg/kg/day) during the sensitization and challenge phases of a murine CHS assay and inflammatory responses were measured. Subsequent assays were performed on mice treated with Neovastat or Cortisone (120 mg/kg/day, IP) and differential mRNA expression of several pro- and antiinflammatory cytokines was quantified using RT-PCR.
  
  
  RESULTS
  Neovastat decreased inflammation by 39% when administered during sensitization but did not alter the CHS response when given during the challenge phase. Neovastat significantly induced IL-10 expression in skin and skin-draining lymph nodes (49% and 45%, respectively) and decreased IFNgamma expression in the lymph nodes (35%).
  
  
  CONCLUSIONS
  Antiinflammatory effects of Neovastat observed in CHS could be linked to modulation of cytokines early in the sensitization phase.
authors.affiliation: AEterna Laboratories, Quebec, Quebec, Canada.
authors.forename: E
authors.initials: E
authors.lastname: Dupont
authors.forename: B
authors.initials: B
authors.lastname: Wang
authors.forename: A J
authors.initials: AJ
authors.lastname: Mamelak
authors.forename: B G
authors.initials: BG
authors.lastname: Howell
authors.forename: G
authors.initials: G
authors.lastname: Shivji
authors.forename: L
authors.initials: L
authors.lastname: Zhuang
authors.forename: V
authors.initials: V
authors.lastname: Dimitriadou
authors.forename: P
authors.initials: P
authors.lastname: Falardeau
authors.forename: D N
authors.initials: DN
authors.lastname: Sauder
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000188:drug therapy*; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014020:Tissue Extracts / Q000494:pharmacology*
chemical_list: D020533:Angiogenesis Inhibitors; D014020:Tissue Extracts; C111481:shark cartilage extract; D016753:Interleukin-10