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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Zymosan-A Induced Peritonitis. Zymosan-A was administered IP (0.25 mg/mouse). Dexamethasone was administered 30 minutes prior to Zymosan-A challenge. Four hours after Zymosan-A challenge, peritoneal lavage fluid was collected; A) Lavage cells were counted and analyzed for number of leukocytes, with differential analysis of neutrophils, lymphocytes, eosinophils, basophils, and monocytes; B) Polymorphonuclear leukocytes (PMN) levels were calculated by summing the number of neutrophils, eosinophils, and basophils; C) Lavage supernatant was analyzed for MCP-1 levels by ELISA.

Zymosan-A challenge caused an increase of leukocytes in the peritoneal cavity, including an increase in PMN levels. In addition, there was an increase in MCP-1 levels in the peritoneal cavity. Pretreatment with dexamethasone (20 mg/kg, PO) caused a significant decrease of leukocyte counts, PMNs, and MCP-1 in the peritoneal lavage fluid compared to the Zymosan A / Vehicle group (n=8/group; * p<0.05, ** p<0.005, *** p<0.001, **** p<0.0001).

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.