Enhancement of survival from murine polymicrobial peritonitis with increased abdominal abscess formation

Abstract

Muramyl dipeptide (MDP), a purified synthetic immune adjuvant, has been shown to increase murine intraabdominal abscess formation in a monomicrobial model using Bacteroides fragilis. This effect required live bacteria and was abolished by appropriate antibiotics. A polymicrobial model of peritonitis and abdominal abscess formation using Streptococcus fecalis, Escherichia coli, and B. fragilis was initially used to determine mortality rates at various concentrations and obtain an appropriate LD 50. Animals were then pretreated with MDP or its inert buffer and underwent intraperitoneal injection of the appropriate bacterial suspension. Mortality and abdominal abscess formation were then assessed at 2 weeks after injection. There was a significant reduction in mortality ( P < 0.03) in mice treated with MDP compared to the controls. In surviving animals, there was also a significant increase in the number of animals forming abscesses ( P < 0.05) following treatment with MDP. This study has shown that nonspecific immune stimulation by MDP provided enhanced protection against a polymicrobial intraperitoneal challenge and paradoxically increased the formation of abdominal abscesses at the same time. This may be regarded as enhancement of the natural history of survival from peritonitis via bacterial containment through intraabdominal abscess formation, a manifestation of beneficial outcome in experimental peritonitis.