Therapeutic effects of LK 423, a phthalimido-desmuramyldipeptide compound,on dextran sulfate sodium-induced colitis in rodents through restoring their interleukin-10 producing capacity

A new phthalimido compound, N-[2-(2- phthalimidoethoxy)acetyl]-L-alanyl-D-g lutamic acid (CAS 142489-47-2, LK 423), was examined for its possible activ ity to modulate levels and species of cytokines in mice carrying a specific inflamed organ. Colonic inflammation was induced in mice by giving 5 % dex tran sulfate sodium (DSS) solution as drinking water. The capacity of splee n cells obtained from the DSS-inflamed mice to produce interleukin-10 (IL-I O) in response to mitogen was significantly reduced when compared with the capacity of spleen cells from Intact mice. Treatment of the mice administer ed DSS by subcutaneous multiple Injections with a low dose of LK423 resulte d in delaying the progression to full-blown inflammation in the colon. The mitogen-stimulated spleen cells obtained from the LK423-treated mice yielde d significantly greater amounts of IL-10 and IL-6 than the untreated DSS gr oup, and the peritoneal cells from the LK423-treated mice produced signific antly lower levels of tumor necrosis factor alpha (TNF alpha). Based on thi s 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 immuno logical characteristics of this new compound are discussed from the point o f view of its possible application as a therapeutic agent for inflammatory bowel diseases (IBD) and other inflammatory diseases.