Inhibitory effects of the new anti-inflammatory agent, IS-741, on spontaneous colitis in HLA-B27/beta2-microglobulin transgenic rats.

Abstract

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.

CONCLUSION:

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.

• Authors: Jin Makino, Akira Andoh, Kazunori Hata, Shuichi Yotsuya, Hiroshi Shikama, Masashi Imamura, Yoshihide Fujiyama, Tadao Bamba
• Journal: Journal of gastroenterology and hepatology (J Gastroenterol Hepatol) Vol. 17 Issue 8 Pg. 854-60 (Aug 2002) ISSN: 0815-9319 [Print] Australia
• PMID: 12164961 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• HLA-B27 Antigen
• Pyridines
• beta 2-Microglobulin
• IS 741

Topics

• Animals
• Animals, Genetically Modified (genetics)
• Anti-Inflammatory Agents (therapeutic use)
• Colitis (drug therapy, genetics, pathology)
• Disease Models, Animal
• HLA-B27 Antigen (genetics)
• Lymphocyte Count
• Male
• Pyridines (therapeutic use)
• Rats (genetics)
• beta 2-Microglobulin (genetics)