Respuesta del sistema inmune a la inducción de peritonitis bacteriana en ratas con cirrosis biliar

Resumo

Background: Bacterial infections are important causes of liver damage progression, development of complications and morbidity and mortality in cirrhosis. Its frequency is related to the immune system dysfunction, the alterations in the intestinal barrier function and the liver failure. Several studies indicate a higher prevalence of bacterial infections in cirrhosis caused mainly by an immune dysfunction. The aim of this study was to investigate whether there is in fact a malfunction of the immune system in rats with bile duct ligation (BDL)-induced cirrhosis that facilitates the development of bacterial infections. Material and methods: We studied bacterial translocation (BT) and dissemination, and the phenotype and activation status of the immune systems cells at the systemic circulation and the peritoneal cavity, in rats with BDL-induced cirrhosis (n=11), BDL-induced cirrhosis and induced bacterial peritonitis (IBP) (n=9), shamoperated rats (n=17) and sham-operated with IBP rats (n=12). Six weeks after inducing cirrhosis by BDL, bacterial peritonitis was induced to rats by intraperitoneal injection of E.coli-ampicilin+. . Two hours later, rats were sacrificed and we examined BT, dissemination and phenotype and activation status of immune cell subpopulations. Results: Experimental cirrhosis is associated with an increased BT rate and higher bacterial dissemination, before and after inducing bacterial peritonitis, when comparing with sham-operated rats. Cirrhotic rats show a systemic proinflammatory state with increased serum levels of TNFα and IFNγ. Ascitic fluid of cirrhotic rats show increased numbers of activated T and B lymphocytes, but a significant retraction of monocytes. TNFα and IFNγ levels in the ascitic fluid of cirrhotic rats are also increased when comparing to those in the peritoneal cavity of controls. IBP causes the systemic retraction of all the immune system populations, but increased serum levels of proinflammatory cytokines. Higher levels of TNFα secreted by Th lymphocytes, but not by monocytes, are detected in the ascitic fluid of cirrhotic rats after IBP. Conclusion: In experimental cirrhosis, TB and dissemination of bacteria, both before and after induced bacterial peritonitis, are increased when comparing with sham-operated rats. This is due to the persistent bacterial stimulus, provoking activation of the immune cells, with an increased production of proinflammatory cytokines, and finally peritoneal and systemic inflammation, which, however is related to a dysfunction in the subpopulation of monocytes. This translates into an altered response of the immune system to the infection.