Interleukin-10 inducing activity of LK423, a phthalimido-desmuramyldipeptide compound

A new phthalimido compound, N-[2-(2-phthalimidoethoxy)acetyl]-L-alanyl-D-gl utamine acid (CAS 142489-47-2, LK423), was examined along with other N-acyl -desmuramyldipeptide compounds for possible immunomodulating activities in cyclophosphamide (Cy)-treated mice. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Northern blot assays demonstrated that multiple subcu taneous injections of LK423 (1 to 50 mu g/day for 4 days) into these mice r esulted in upregulating interleukin-10 (IL-10) gene expression in the splee n. In contrast to IL-10, expression of interferon-gamma (IFN-gamma) gene wa s reduced by treating with this compound. The culture supernatant of spleen cells obtained from the mice that had received LK423 injections was found to contain a larger amount of IL-10 protein than in the culture supernatant of the spleen obtained from the mice that received no LK423 injections whe n tested by enzyme-linked immunosorbent assay (ELISA). Conversely to IL-10, the concentration of IFN-gamma was lower in the culture supernatant from t he LK423-treated group than that in the control group. In contrast to this compound, other N-acyl-desmuramyldipeptide derivatives carrying a L-alanyl- D-isoglulamine moiety, and other immunological stimulants showed an activit y to augment production of IFN-gamma and reduce the gene expression of IL-1 0. The immunological activities of this new phthalimido desmuramyldipeptide compound, LK423, are discussed from the point of view of its therapeutic a pplication.