Modulation of the contact hypersensitivity response by AE-941 (Neovastat), a novel antiangiogenic agent.
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.
Dupont
E
E
AEterna Laboratories, Quebec, Quebec, Canada.
Wang
B
B
Mamelak
A J
AJ
Howell
B G
BG
Shivji
G
G
Zhuang
L
L
Dimitriadou
V
V
Falardeau
P
P
Sauder
D N
DN
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*
D020533:Angiogenesis Inhibitors; D014020:Tissue Extracts; C111481:shark cartilage extract; D016753:Interleukin-10