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Enhancement of survival from murine polymicrobial peritonitis with increased abdominal abscess formation
W G Cheadle1, M J Hershman, B Mays
1Department of Surgery, University of Louisville School of Medicine, Kentucky 40292.
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 LD50. 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 less than 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 less than 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.
Insights
Muramyl dipeptide (MDP) enhances survival against polymicrobial peritonitis by promoting abscess formation. This immune stimulation paradoxically aids bacterial containment, improving outcomes in experimental peritonitis.
Area of Science:
- Immunology
- Microbiology
- Surgical Infection Models
Background:
- Muramyl dipeptide (MDP) is a synthetic immune adjuvant.
- MDP has been shown to increase intraabdominal abscess formation in monomicrobial models.
- The role of MDP in polymicrobial peritonitis requires further investigation.
Purpose of the Study:
- To evaluate the effect of MDP on mortality and abscess formation in a polymicrobial peritonitis model.
- To determine the LD50 of a polymicrobial bacterial suspension for use in experimental peritonitis.
- To assess the protective potential of MDP against a complex bacterial challenge.
Main Methods:
- Establishment of a polymicrobial peritonitis model using Streptococcus fecalis, Escherichia coli, and Bacteroides fragilis.
- Determination of LD50 and appropriate bacterial concentrations for challenge.
- Pretreatment of mice with MDP or buffer prior to intraperitoneal bacterial injection.
- Assessment of mortality rates and intraabdominal abscess formation at 2 weeks post-injection.
Main Results:
- MDP pretreatment significantly reduced mortality in mice challenged with polymicrobial peritonitis (P < 0.03).
- MDP treatment led to a significant increase in abscess formation in surviving animals (P < 0.05).
- MDP demonstrated enhanced protection against a polymicrobial intraperitoneal challenge.
Conclusions:
- Nonspecific immune stimulation with MDP provides enhanced protection against polymicrobial peritonitis.
- MDP paradoxically increases intraabdominal abscess formation, which may represent beneficial bacterial containment.
- Abscess formation induced by MDP can be interpreted as a favorable outcome in experimental peritonitis, enhancing survival.