Therapeutic effects of LK 423, a phthalimido-desmuramyl-dipeptide compound, on dextran sulfate sodium-induced colitis in rodents through restoring their interleukin-10 capacity = Therapeutische Wirkungen des Phthalimido-desmuramyldipeptid-Derivats LK423 auf die Dextransulfat-Natrium-induzierte Kolitis bei Nagetieren durch Wiederherstellung ihrer Fähigkeit zur Interleukin-10-Produktion
Moriguchi, Miho ...
A new phthalimido compound, N-[2-(2-phthalimidoethoxy)acetyl]-L-alanyl-D-glutmaic 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 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 amount of IL-10 and IL-6 than untreated DSS group, and the peritonealcells from the LK423-treated mice produced significantly lower levels of tumor necrosis factor [alpha] TNF[alpha].Based on this prophylactyc effect of LK423 in the murine colitis model, its therapeutic effect was examined in rates 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 diminshing the ulcerative area in the colon. The immunological characteristics of this new compound are discused from the point of view of its possible application as a therapeutic agent for inflammatory bowel disease(IBD) and other inflammatory diseases.
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