Inhibitory effects of the new anti-inflammatory agent, IS-741, on spontaneous colitis in HLA-B27/beta2-microglobulin transgenic rats.
BACKGROUND
A novel anti-inflammatory drug, IS-741, blocked the adhesion of inflammatory cells to microvascular endothelial cells both in vivo and in vitro. Transgenic rats expressing human leukocyte antigen (HLA)-B27 and human beta2-microglobulin (HLA-B27 rats) spontaneously develop chronic colitis, which resembles human inflammatory bowel disease. In the present study, the authors examined the efficacy of IS-741 against spontaneous colitis in HLA-B27 rats.


METHODS
The HLA-B 27 rats were divided in two groups after the development of colitis. IS-741 was dissolved in water and administered orally (10 mg/kg) once per day for 14 days.


RESULTS
The HLA-B27 rats treated with IS-741 remained healthy; the wet weight of the colon was significantly lower in the IS-741-treated group. Histological examinations revealed a marked infiltration of inflammatory cells into both the mucosa and the submucosa in the control HLA-B27 rats, but these changes were attenuated in the IS-741-treated group. The mucosal damage score was also significantly reduced by treatment with IS-741. IS-741 significantly reduced the mucosal myeloperoxidase activity and mucosal cytokine-induced neutrophil chemoattractant-1 levels. IS-741 also reduced CD3-positive T-cell infiltration.


CONCLUSIONS
IS-741 suppressed the spontaneous colitis that developed in HLA-B27 rats. Some of the actions of IS-741 may be associated with its inhibitory effects on the adhesion of neutrophils to endothelial cells. The findings from the present study suggest that IS-741 may be a useful new therapeutic agent for inflammatory bowel disease.
Makino
Jin
J
Division of Gastroenterology, Shiga University of Medical Science, Otsu, Japan.
Andoh
Akira
A
Hata
Kazunori
K
Yotsuya
Shuichi
S
Shikama
Hiroshi
H
Imamura
Masashi
M
Fujiyama
Yoshihide
Y
Bamba
Tadao
T
D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D003092:Colitis / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D015796:HLA-B27 Antigen / Q000235:genetics*; D018655:Lymphocyte Count; D008297:Male; D011725:Pyridines / Q000627:therapeutic use*; D051381:Rats / Q000235:genetics; D001613:beta 2-Microglobulin / Q000235:genetics*
D000893:Anti-Inflammatory Agents; D015796:HLA-B27 Antigen; D011725:Pyridines; D001613:beta 2-Microglobulin; C097462:IS 741