Roquinimex inhibits dextran sodium sulfate-induced murine colitis.
OBJECTIVE
Roquinimex is a modulator of the immune system and has been shown to attenuate induction of several inflammatory and autoimmune diseases. The objective of the present study was to determine the efficacy of roquinimex in a model of murine colitis.


METHODS
For this purpose, Balb/c mice were exposed to 5% dextran sodium sulfate (DSS) in the drinking water for five to six days. Roquinimex (300 mg kg(-1) day(-1)) was administered by subcutaneous (s.c.) injection 3 days prior to and throughout the treatment period with DSS. In separate experiments, 300 mg kg(-1) day(-1) of roquinimex was given therapeutically after initiation of DSS challenge.


RESULTS
DSS provoked clinical signs of colitis, reduced crypt height (CH) and increased mucosal damage score (MDS) as analyzed by histology. In addition, challenge with DSS increased the colonic content of myeloperoxidase (MPO). Prophylactic administration of DSS-treated mice with roquinimex significantly reduced clinical signs of colitis, MDS and the CH-reduction. Moreover, in roquinimex treated animals, the MPO activity was significantly reduced by more than 50% compared to DSS control mice. Notably, therapeutic administration of roquinimex in DSS-treated mice also significantly inhibited the MDS, CH-reduction and MPO activity.


CONCLUSIONS
These findings suggest that roquinimex strongly inhibits murine colitis and may provide a novel pharmacological approach to treat inflammatory bowel disease.
Liu
Q
Q
Department of Surgery, Malmö University Hospital, Lund University, 20502 Malmö, Sweden.
Wang
Y
Y
Wan
M X
MX
Zhang
X W
XW
Andersson
G
G
Hedlund
G
G
Thorlacius
H
H
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D003106:Colon / Q000201:enzymology / Q000473:pathology; D016264:Dextran Sulfate; D006912:Hydroxyquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000037:antagonists & inhibitors
D000276:Adjuvants, Immunologic; D006912:Hydroxyquinolines; C045282:roquinimex; D016264:Dextran Sulfate; D009195:Peroxidase