Abstract |
A new phthalimido compound, N-[2-(2-phthalimidoethoxy)acetyl]-L-alanyl-D- glutamic acid (CAS 142489-47-2, LK 423), was examined for its possible activity to modulate levels and species of cytokines in mice carrying a specific inflamed organ. Colonic inflammation was induced in mice by giving 5% dextran sulfate sodium (DSS) solution as drinking water. The capacity of spleen cells obtained from the DSS-inflamed mice to produce interleukin-10 (IL-10) in response to mitogen was significantly reduced when compared with the capacity of spleen cells from intact mice. Treatment of the mice administered DSS by subcutaneous multiple injections with a low dose of LK423 resulted in delaying the progression to full-blown inflammation in the colon. The mitogen-stimulated spleen cells obtained from the LK423-treated mice yielded significantly greater amounts of IL-10 and IL-6 than the untreated DSS group, and the peritoneal cells from the LK423-treated mice produced significantly lower levels of tumor necrosis factor alpha ( TNF alpha). Based on this prophylactic effect of LK423 in the murine colitis model, its therapeutic effect was examined in rats in which colitis had been induced by feeding 3% DSS for 12 days. Intracolonic administration of LK423 to these rats for 7 days resulted in diminishing the ulcerative area in the colon. The immunological characteristics of this new compound are discussed from the point of view of its possible application as a therapeutic agent for inflammatory bowel diseases (IBD) and other inflammatory diseases.
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Authors | M Moriguchi, K Urabe, N Norisada, C Ochi, A Stalc, U Urleb, S Muraoka |
Journal | Arzneimittel-Forschung
(Arzneimittelforschung)
Vol. 49
Issue 2
Pg. 184-92
(Feb 1999)
ISSN: 0004-4172 [Print] Germany |
PMID | 10083986
(Publication Type: Journal Article)
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Chemical References |
- Adjuvants, Immunologic
- Dipeptides
- Phthalimides
- Tumor Necrosis Factor-alpha
- Interleukin-10
- N-(2-(2-phthalimidoethoxy)acetyl)-L-alanyl-D-glutamic acid
- Dextran Sulfate
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Topics |
- Adjuvants, Immunologic
(pharmacology)
- Animals
- Cells, Cultured
- Colitis
(chemically induced, drug therapy, pathology)
- Colitis, Ulcerative
(chemically induced, drug therapy, pathology)
- Colon
(pathology)
- Dextran Sulfate
- Dipeptides
(pharmacology)
- Female
- Interleukin-10
(biosynthesis)
- Mice
- Mice, Inbred BALB C
- Occult Blood
- Peritoneal Cavity
(cytology)
- Phthalimides
(pharmacology)
- Rats
- Rats, Inbred Strains
- Spleen
(drug effects, metabolism, pathology)
- Tumor Necrosis Factor-alpha
(biosynthesis)
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