Priming effect of orally administered muramyl dipeptide on induction of endogenous tumor necrosis factor.

Orally administered muramyl dipeptide (MDP) was found to prime induction of endogenous tumor necrosis factor (TNF) in mice. This priming effect was observed after oral administration of MDP of more than 100 micrograms/mouse; the maximal time interval between oral administration of MDP and i.v. injection of OK-432, a triggering agent for induction of endogenous TNF, was extended over 3-10 h and then decreased after 24 h. Antitumor effect against Meth-A, MH134, and MM46 tumor cells in mice was observed after oral administration of MDP followed by i.v. injection of OK-432. These findings suggest that orally administered MDP can be used as a priming agent for inducing endogenous TNF in cancer patients, and that MDP, a component of enteric bacteria, must have an important role in maintaining homeostasis through activation of macrophages.