Induction of tumor necrosis factor-alpha in solid tumor region by the orally administered synthetic muramyl dipeptide analogue, romurtide.

The novel applications of a muramyl dipeptide analogue, romurtide, were investigated. When mice were intravenously injected with 10-1000 micrograms/mouse of romurtide as a primer and 3 KE/mouse of OK-432 as a trigger, systemic tumor necrosis factor-alpha (TNF-alpha) activity was increased. Similar effects were also detected by oral administration of romurtide at 1000 to 10,000 micrograms/mouse. These effects reached maximum at 3 h (intravenous injection, i.v.) or 6 h (oral administration, p.o.) after administration and were sustained for 48 h. When romurtide was administered to MM46 tumor-bearing mice orally, the significant augmentation of TNF-alpha production could be detected in the solid tumor and the liver. When romurtide was intravenously injected to the tumor bearer, the TNF-alpha production was significantly augmented in the spleen. These findings suggest that romurtide can augment the host defense system by both the parenteral and oral route, and indicate the possibility of a new type of anti-tumor therapy to induce TNF-alpha in the tumor region.