Nonspecific Enhancement of Resistance to Bacterial Infection

Abstract

Experiments have been undertaken to further characterize the actions of the synthetic immunoadjuvant compound, muramyl dipeptide (MDP), in an animal model simulating surgical infection. When used prophylactically in combination with antibiotics, MDP proved to be significantly additive in terms of local and systemic effects, and survival, to both chloramphenicol (p less than 0.01) and cephaloridine (p less than 0.05). The combined use of MDP and cephaloridine therapy, initiated four or six hours following infectious challenge and including a surgical foreign body in starved and refed animals, showed statistically significant decreases in bacteremia during early time periods, as well an increased early survival (p less than 0.02), compared with the use of cephaloridine alone. Benefits observed in the therapeutic mode were of lesser magnitude than those observed following prophylactic use, but the model used was a much more significant physiologic challenge. Evidence indicating additive effects to those of antibiotics is essential prior to the use of MDP in clinical trials.

Prevention of oncogenic viral infections in mice with CGP 11637, a synthetic muramyl dipeptide analog

“…This supports previous observations that MDP and its analogs act nonspecifically against a variety of infectious agents (4,10,13,14,(20)(21)(22).…”

“…The tumors studied were blood cell malignancies induced by Friend Muramyl dipeptide (MDP), N-acetyl-muramyl-L-alanyl-Disoglutamine, a dipeptide derivative of muramic acid (the 3-0-D-lactyl ether of D-glucosamine), is a typical bacterial cell wall constituent that represents the minimal sequence of peptidoglycans that still retains the full activity of Freund complete adjuvant in augmenting humoral immune responses (17,(20)(21)(22)31).A series of synthetic MDP analogs have been synthesized, and it has been found that by substitution of component carbohydrates and amino acids, pyrogenicity and other inflammatory and toxic side effects of MDP can be diminished or totally eliminated without loss of effectiveness (5,8,31). Synthetic MDP and its analogs have been shown to act as macrophage activators (4,9,10,13,26,28,29,32,33) and to effect some control of neoplastic spread in experimental systems as well as in various viral, bacterial, and fungal infections (2, 9, 10, 13-15, 18, 20-22, 24, 29).…”

“…Muramyl dipeptide (MDP), N-acetyl-muramyl-L-alanyl-Disoglutamine, a dipeptide derivative of muramic acid (the 3-0-D-lactyl ether of D-glucosamine), is a typical bacterial cell wall constituent that represents the minimal sequence of peptidoglycans that still retains the full activity of Freund complete adjuvant in augmenting humoral immune responses (17,(20)(21)(22)31).…”

Roles of peripheral leukocytes and tissue macrophages in antibacterial resistance induced by free or liposome-encapsulated muramyl tripeptide phosphatidylethanolamide

“…Increased resistance against experimental K. pneumoniae infection due to treatment with muramyl dipeptide (MDP) or derivatives thereof was observed by several investigators (1,3,8,18,22,25,26). The precise mechanisms by which muramyl peptides exert their protective effects remain incompletely understood.…”

“…at 24 h before i.p. inoculation with 103 K. pneunmniae with 50 ,ug of MTPPE,25 p.g of LE-MTPPE, PBS, or empty liposomes (EL).b Log number of leukocytes in 4 ml of peritoneal wash fluid. FII), or empty liposomes ) ).Each point represents the geometric mean for six mice ± standard error of the mean.…”