Effect of Free and Liposome-Encapsulated MTP-PE on Klebsiella pneumoniae Infection in Mice

Abstract

In immunocompromised patients infections freguently occur, and treatment of these infections is not always successful. In these patients the antimicrobial resistance at the site of infection is insufficient, resulting in the appearance of bacteria in the blood. Increasing the capacity of the mononuclear phagocyte system (MPS) to effective elimination of bacteria from the blood may be of great value for these patients. This may be realized by administration of the immunomodulator muramyl tripeptide (MTPPE). MTPPE is a lipophilic derivative of muramyl dipeptide, the minimal active structure that can substitute for Mycobacteria in Freund’s complete adjuvans (Ellouz and others, 1974). Because the appearance of bacteria in the blood in immunocompromised patients occurs at regular intervals they need to be protected for a longer period. Regular administration of MTPPE is expected to result in toxic side effects (Schumann and others, 1989). Reduction of toxicity may be accomplished by encapsulation of MTPPE in liposomes, which are taken up preferably by the cells of the MPS. The question is whether liposome-encapsulated MTPPE (LE-MTPPE) retains its activity. LE-MTPPE has proven to be beneficial in in-vitro and in-vivo models of tumorcytotoxicity and microbial infections (Gangemi and others, 1987, Koff and others, 1985, Talmadge and others, 1986, Fidler and others, 1985).