Zymosan-Induced Peritonitis

Abstract

Zymosan-induced peritonitis is a model commonly used to study systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). However, effects of zymosan on cardiac function have not been reported. We evaluated cardiac responses to zymosan in mice and the role of β-glucan and dectin-1 in mediating these responses. Temperature and cardiac function were evaluated before and after intraperitoneal (i.p.) injection of zymosan (100 or 500 mg/kg) or saline. Chronotropic and dromotropic functions were measured using electrocardiograms collected from conscious mice. Cardiac inotropic function was determined by echocardiography. High-dose zymosan caused rapid and maintained hypothermia along with visual signs of illness. Baseline heart rate (HR) was unaffected but HR variability increased, and there was a modest slowing of ventricular conduction. High-dose zymosan also caused prominent decreases in cardiac contractility at 4 and 24 h. Since zymosan is known to cause gastrointestinal tract pathology, peritoneal wash and blood samples were evaluated for bacteria at 24 h after zymosan or saline injection. Translocation of bacterial occurred in all zymosan-treated mice (n=3), and two had bacteremia. Purified β-glucan (50 and 125 mg/kg, i.p.) had no effect on temperature or ECG parameters. However, deletion of dectin-1 modified the ECG responses to high-dose zymosan; slowing of ventricular conduction and the increase in HR variability were eliminated but a marked bradycardia appeared at 24 h post-zymosan treatment. Zymosan-treated dectin-1 knockout mice also showed hypothermia and visual signs of illness. Fecal samples from dectin-1 knockout mice contained more bacteria than wild types, but zymosan caused less translocation of bacteria. Collectively, these findings demonstrate that zymosan induced systemic inflammation causes cardiac dysfunction in mice. The data suggest that dectin-1 dependent and independent mechanisms are involved. While zymosan treatment causes translocation of bacteria this effect does not have a major role in the overall systemic response to zymosan.

Anti-inflammatory Property of Imperatorin on Alveolar Macrophages and Inflammatory Lung Injury

“…20 When injected into animals, zymosan induces inflammation by a series of mechanisms leading to severe organ dysfunction syndrome. 21 Lung injury was characterized by alveolar thickening, infiltration of immune cells, and increased permeability of the alveolar capillary membrane. 22,23 As shown in Figure 1A, the mice in the sham and imperatorin-treated alone groups showed no morphologic changes after H&E staining, indicating that intraperitoneal administration of saline or imperatorin alone did not induce additional response in this experimental procedure.…”

The Role of NLRP3 Inflammasome in Pericarditis

“…Based on literature, zymosan A was shown to induce NLRP3 inflammasome activation ( 12 , 13 , 14 , 15 ), and here we used it to develop a mouse model of acute pericarditis. In order to assess induction of pericarditis, we evaluated 3 parameters reflecting inflammation of the pericardium: presence of pericardial effusion, pericardial thickness, and ASC expression.…”

“…Zymosan A is a cell wall extract from the yeast Saccharomyces cerevisiae and a known agonist of the TLR-2 (toll-like receptor-2). Zymosan A leads to the activation of the NLRP3 inflammasome ( 13 ) and was already used in mouse models of peritonitis and arthritis ( 14 , 15 ).

Figure 1 Schematic Representation of the Experimental Mouse Model of Acute Pericarditis Under general anesthesia, 1 mg of zymosan A (in 50 μl of sterile NaCl 0.9%) was injected in the pericardial sac of the mouse on day 0.

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Xiphoid Surface Temperature Predicts Mortality in a Murine Model of Septic Shock

“…Mice become hypothermic in sepsis, proportional to the severity of infection (5–6), and changes in core temperature have previously been employed as markers of recovery (7–10). However, in most cases the experimental methods have been impractical, as core temperature was monitored by insertion of a rectal probe, which can induce additional stress, or by surgical placement of a telemetric thermometer.…”