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Colon Ascendens Stent Peritonitis CASP - a Standardized Model for Polymicrobial Abdominal Sepsis
Published on: December 19, 2010
Polysaccharide-mediated protection against abscess formation in experimental intra-abdominal sepsis
A O Tzianabos1, D L Kasper, R L Cisneros
1Channing Laboratory, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Abstract:
Abscess formation is a major complication of intra-abdominal sepsis that causes significant morbidity and mortality. In such cases, Bacteroides fragilis is the predominant anaerobic isolate. In a rat model of intra-abdominal sepsis, the capsular polysaccharide complex (CPC) from B. fragilis promotes abscess formation and when administered sub-cutaneously, protects against this host response by a T cell-dependent immune mechanism. In the present study, the polysaccharide A (PS A) component of CPC protected animals against challenge with live heterologous bacterial species (mixtures of anaerobes and facultative organisms) that are most commonly isolated from intra-abdominal abscesses in humans. Protection against heterologous bacterial challenge was transferred by T cells. Administration of PS A shortly before or even after challenge with B. fragilis protected against this host response. In experiments designed to simulate fecal contamination of the human peritoneal cavity, PS A protected animals against abscess formation induced by a rat cecal contents inoculum. The surprisingly broad protective activity of PS A indicates that this molecule is likely suppressing a nonspecific host tissue reaction that forms in response to a variety of abscess-inducing organisms and that it might be useful in preventing abscess formation associated with intra-abdominal sepsis in the clinical setting.
Insights
Polysaccharide A (PS A) from Bacteroides fragilis prevents abscess formation in a rat model. This immune molecule offers broad protection against various bacteria, suggesting clinical potential for intra-abdominal sepsis.
Area of Science:
- Immunology
- Microbiology
- Sepsis Research
Background:
- Intra-abdominal sepsis frequently leads to abscess formation, a significant cause of illness and death.
- Bacteroides fragilis is a common bacterial isolate in these abscesses.
- The capsular polysaccharide complex (CPC) of B. fragilis is known to promote abscess formation but can induce a protective T cell-dependent immune response when administered subcutaneously.
Purpose of the Study:
- To investigate the protective role of polysaccharide A (PS A), a component of CPC, against abscess formation.
- To determine if PS A can protect against challenge with bacteria commonly found in human intra-abdominal abscesses.
- To evaluate the efficacy of PS A in a simulated fecal contamination model of intra-abdominal sepsis.
Main Methods:
- Administered PS A to rats in a sepsis model.
- Challenged animals with live heterologous bacterial species and B. fragilis.
- Assessed protection against abscess formation induced by fecal contents inoculum.
- Investigated the role of T cells in mediating protection.
Main Results:
- PS A conferred protection against challenge with diverse bacterial species commonly found in human intra-abdominal abscesses.
- Protection mediated by PS A was transferable via T cells.
- PS A administration, even after bacterial challenge, effectively prevented abscess formation.
- PS A demonstrated protective effects in a rat model simulating fecal contamination.
Conclusions:
- Polysaccharide A exhibits broad protective activity against abscess formation induced by various bacteria.
- PS A appears to suppress a non-specific host tissue reaction involved in abscess development.
- PS A holds potential as a therapeutic agent for preventing abscesses in clinical settings of intra-abdominal sepsis.
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