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Purpose: There is a lack of clinical evidence supporting the use of lavage in patients with peritonitis. It is known that fluids such as normal saline cause temporary damage to the peritoneum and that increased production of proinflammatory mediators is associated with a poor outcome. This study used an experimental model to evaluate the effect of lavage on the peritoneal mesothelium and the ability of peritoneal mesothelial cells to produce a battery of proinflammatory mediators (TNFalpha, IL-1beta, GROalpha, and ICAM-I.)., Methods: Wistar rats were allocated into four groups (control, peritonitis, lavage, peritonitis plus lavage). Peritonitis was induced by exposure to zymosan and saline was used for lavage. After 18, 24, and 43 hours, mesothelial imprints were taken from the peritoneum for histology, semiquantitative reverse transcription-polymerase chain reaction, Western blot analyses, and immunocytochemistry., Results: Both peritonitis and lavage caused peritoneal damage at 18 and 24 hours, and this effect was additive. At varying times, peritoneal mesothelial cells from animals undergoing lavage had greater up-regulation (P < 0.05) of mRNA expression for TNFalpha, IL-1beta, GROalpha, and ICAM-I and greater production (P < 0.05) of TNFalpha, IL-1RII, GROalpha, and ICAM-I. The latter was heavily concentrated at the cell membrane., Conclusions: Lavage causes self-limiting peritoneal damage and this is associated with an up-regulation of proinflammatory mediators in animals with peritonitis.

Background: Many of the effector mechanisms that characterize peritonitis are generated by neutrophils and macrophages. However, it is now appreciated that peritoneal mesothelial cells can also produce mediators of inflammation when grown in culture. This study tested the hypothesis that peritoneal mesothelial cells produce inflammation-related cytokines in a murine model of peritonitis., Methods: Fifty Wistar rats were randomized to either a control group or a peritonitis group. Groups of five animals were sacrificed at 4, 18, 24, 48, and 96 h after the induction of peritonitis, which was induced by the administration of 5 mg zymosan intra-peritoneally. Control animals received an equal volume of phosphate-buffered saline. Monolayers of peritoneal mesothelial cells were obtained using an imprint technique. The expression and production of TNFalpha, IL-1beta, IL-10, and ICAM-I were determined using semi-quantitative reverse transcription- polymerase chain reaction, immunocytochemistry, and Western blotting., Results: The mesothelial cells significantly expressed TNFalpha, IL-1beta, IL-10, and ICAM-I in a time-dependent manner. We were able to demonstrate increased production for each of these cytokines, and this coincided with the initial shedding of mesothelial cells and their regeneration within 96 h., Conclusions: Peritoneal mesothelial cells play a role in peritonitis by producing inflammation- associated cytokines. This implies that they may be suitable targets for molecular interventions aimed at modulating the effects of peritonitis.

Introduction: The production of nitric oxide is an important peritoneal defense mechanism. We have evaluated the effect of various putative stimulants on nitric oxide production by peritoneal mesothelial cells., Methods: Wistar rats were randomized to either a control group or a peritonitis group (5 mg zymosan intraperitoneally). Groups of five animals were sacrificed at 4, 18, 24, 48 and 96 h after the induction of peritonitis and their peritoneal fluid was harvested for assay. Cultures of peritoneal mesothelial cells were stimulated with lipopolysaccharide, myeloperoxidase, TNFalpha, zymosan, peritoneal fluid from a control animal and peritoneal fluid from a peritonitis animal. Supernatants were collected after incubation for 4, 24 and 48 h for assay. The assay for nitric oxide was based upon the nitrite content of the samples., Results: The intraperitoneal administration of zymosan was associated with an increased production of nitric oxide (NO) when compared with control animals (P < 0.01). In cultures of peritoneal mesothelial cells, zymosan, but not the other putative stimulants, was associated with a marked output of nitric oxide (P < 0.001)., Conclusion: Zymosan has a direct effect on peritoneal mesothelial cells, which are able to generate nitric oxide in the absence of co-stimulatory molecules. This suggests that it may be possible to use some form of external stimulation to up-regulate the NO response by peritoneal mesothelial cells.

Introduction: Patients with peritonitis often exhibit systemic manifestations of sepsis, especially in the lungs. The aim of the present study was to evaluate the local and systemic effects of the neutrophil response to peritonitis in a rat model., Methods: Fifty Wistar rats were randomized to either a control group or a peritonitis group (5 mg zymosan intraperitoneal). Groups of five animals were killed at 4, 18, 24, 48 and 96 h for evaluation of the morphology of the peritoneum (mesothelial imprint), the number and phenotype of cells within peritoneal fluid (flow cytometry), and myeloperoxidase activity within the peritoneal fluid and distant organs (enzyme assay)., Results: Zymosan produced macroscopic evidence of peritonitis and on microscopy there was disruption of peritoneal mesothelial cells. This was accompanied by an influx of neutrophils between 4 and 48 h (P < 0.001) and macrophages between 48 and 96 h (P < 0.001). There was also an increase in myeloperoxidase activity within peritoneal fluid between 4 and 48 h (P < 0.05), the lung at 4 h (P < 0.01) and the liver at 48 h (P < 0.001)., Conclusion: The present study has confirmed the validity of using zymosan to create a low-morbidity model of peritonitis. Besides the anticipated peritoneal response, there were distant effects of neutrophil activation within the lungs and liver. In the future, strategies that modulate neutrophil activation within these organs might play a useful adjunctive role in the management of patients with peritonitis.

Background: Peritoneal mesothelial cells have a remarkable capacity to respond to peritoneal insults. They generate an intense biological response and play an important role in the formation of adhesions. This review describes these activities and comments on their relationship to surgical drainage, peritoneal lavage and laparostomy in the management of patients with peritonitis., Methods and Results: Material was identified from previous review articles, references cited in original papers and a Medline search of the literature. The peritoneal mesothelium adapts to peritonitis by facilitating the clearance of contaminated fluid from the peritoneal cavity and inducing the formation of fibrinous adhesions that support the localization of contaminants. In addition, the fluid within the peritoneal cavity is a battleground in which effector mechanisms generated with the involvement of peritoneal mesothelial cells meet the contaminants. The result is a complex mix of cascading processes that have evolved to protect life in the absence of surgery., Conclusion: Future advances in the management of patients with severe peritonitis may depend upon molecular strategies that modify the activity of peritoneal mesothelial cells., (Copyright 2003 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Purpose: Peritonitis continues to be a major source of mortality and morbidity in patients undergoing abdominal surgery. The aim of this study was to develop a nonfatal model of bacterial peritonitis in mice so that we could study aspects of the pathobiology and treatment of peritonitis in an in vivo model., Methods: Mice were inoculated via a midline laparotomy with 0.5 mg of zymosan in 0.1 ml of saline into the subomental space. At 24, 48, and 96 hours after treatment, animals were killed, and analysis was performed to determine the degree of peritoneal inflammation. End points included intraperitoneal cellular influx, tumor necrosis factor-alpha concentrations, and myeloperoxidase activity. In addition, peritoneal lavage fluid was plated onto blood agar for analysis of bacterial colony-forming units. There were 40 mice in each group., Results: There were no deaths in either group. Facultative Gram-negative bacteria were cultured from the peritoneal cavities of zymosan-treated animals at 24 and 48 hours after insult (colony-forming unit counts of 92+/-11 vs. 0 in control animals). In the zymosan-treated animals, there were significantly increased numbers of inflammatory cells (especially neutrophils) in the peritoneal cavity at 24 and 48 hours after treatment; these numbers returned to control levels by 96 hours. Myeloperoxidase activity was also elevated both in the peritoneal fluid (2.4 X 10(-4) units/ml compared with 1.6 x 10(-4) units/ml, P < 0.05) and in remote organs (i.e., lung, P < 0.05; liver, P < 0.001; and kidney, P < 0.05) at 24 hours after treatment. There was no significant difference in tumor necrosis factor-alpha levels between zymosan-treated and control mice in either serum or peritoneal fluid at any time point investigated. There was no mortality in either the zymosan-treated or control animals., Conclusion: In this model of bacterial peritonitis in mice, we have demonstrated how the peritoneal cavity can resolve a relatively localized inflammatory insult within 96 hours of induction. This response is characterized by a cellular influx of predominantly neutrophils and macrophages and by pronounced oxidative activity. We will use this in vivo model to characterize aspects of the pathobiology and treatment of peritonitis.

The peritoneum is more than a mechanical covering that allows for the easy gliding of opposed peritoneal surfaces. The peritoneal mesothelial cells facilitate the action of powerful innate immune mechanisms. In addition, the peritoneal-associated lymphoid tissues contain unique cells that may play a crucial role in the localization of intraperitoneal infection. A clearer understanding of the molecular and cellular events underlying peritoneal functions in both the unstimulated and stimulated state will aid future treatment of peritonitis.

Background Bacterial translocation from the gut may occur under a variety of different clinical circumstances and has been implicated in the development of multiple organ failure. The aim of this study was to determine the distribution of bacterial translocation occurring in a model of chemically induced peritonitis. We also sought to document the degree of the associated immune and inflammatory response. Methods Though a midline laparotomy, rats were injected with 5 mg of zymosan (in 0.2 ml of saline) into the subomental space. After 4, 18, 24, 48 and 96 h, a number of endpoints evaluated: intraperitoneal cellular influx, TNF-α and interleukin-6 concentrations and myeloperoxidase activity. Bacterial cultures were initiated from the free peritoneal fluid, mesenteric lymph nodes, liver, lung, and kidney. Imprints were also made of the peritoneal mesothelial surface to determine its integrity. Results When comparing rats injected with zymosan with the controls, there was evidence of a peritoneal inflammatory response within 4 hours. Facultative gram negative bacteria were found to be growing in the mesenteric lymph nodes and in the peritoneal fluid at 48 h. Anaerobic organisms were also cultured from the peritoneal fluid at 48 h. No organisms were cultured from the liver, lung or kidneys. In addition there was a significant increase in intraperitoneal cell numbers (predominantly neutrophils, P < 0.05), myeloperoxidase activity (P < 0.05) and TNF-α and IL-6 concentrations (P < 0.05). There was extensive loss of the peritoneal mesothelial cells. The peritoneal inflammatory changes and bacterial translocation had resolved by 96 h. Conclusion Bacterial translocation can be induced by the presence of an acute inflammatory focus in the peritoneal cavity. The translocation and inflammatory changes were associated with extensive loss of mesothelial cells. Nonetheless, these changes all resolved, indicating that the peritoneal cavity has a significant capacity to... [ABSTRACT FROM AUTHOR]