Zymosan - A Induced Acute Peritonitis Model

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Leukocyte infiltration into a site of injury or irritation is an integral part of an inflammatory process associated with the peritonitis response. The peritonitis model described below utilizes Zymosan-A to induce leukocyte accumulation in the peritoneum. This model can be utilized as a model of inflammation, acute peritonitis and polymorphonucleocyte migration. Importantly, this model is an effective for detecting a test compound’s ability to attenuate inflammatory processes associated with peritonitis. Anti-inflammatory agents including steroidal and non-steroidal anti-inflammatory compounds are effective in reducing leukocyte recruitment and/or infiltration in this model. In the study described below, leukocyte infiltration was induced by intraperitoneal administration of Zymosan-A and the responsiveness of this model to the steroid prednisone was measured. This study validates the use of this model for detecting compounds that are potential therapeutics for peritonitis

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Total number of leukocytes in the peritoneum of untreated and zymosan-a treated mice with or without dexamethosone treatment.

Zymosan-A was administered i.p. (1 mg/mouse). Prednisone was administered 30 minutes prior to Zymosan-A challenge. Four hours after Zymosan-A challenge the peritoneum was lavaged with 5 mL of saline supplemented with heparin (1%). The lavaged fluid was analyzed for levels leukocytes with differential analysis of neutrophils, lymphocytes eosinophils, basophils and monocytes. Polymorphonuclear leukocytes (PMN) levels were calculated by summing the number of neutrophils, eosinophils and basophils (data not shown). Prednisone administration significantly reduced the levels of total leukocytes. **Indicates statistically significant difference from untreated control (p<0.01). + Indicates statistically significant difference from vehicle treated control (p<0.05) (N=6)

The zymosan induced peritonitis model is typically run in an acute setting, performed in a single day with a single administration of test article. As a model of peritonitis it is similar to the Monocyte Infiltration model.