This contention is supported by (1) abrogation by nonabsorbable

antibiotics of the ongoing proinflammatory immune response in MLNs, but not in HLNs or peripheral blood, and (2) direct correlation between HLNs and blood proportions of recently activated Th cells and inflammatory monocytes. Thus, activated immune cells that leave the HLNs and recirculate in peripheral blood preferentially account for the systemic immune activation LY2109761 solubility dmso observed in rats with preascitic cirrhosis. Our detection of passage of bacterial DNA fragments to the MLNs in rats with preascitic cirrhosis is of particular interest. To date, viable (i.e., positive culture) or nonviable (i.e., DNA fragments) bacteria in the MLNs had only been reported in rats with cirrhosis and ascites.6, 11, 16, 27 Similarly, passage of enteric bacterial products to the bloodstream, as shown by increased serum lipopolysaccharide-binding protein or bacterial DNA in serum, has only been demonstrated in patients with cirrhosis and ascites.3, 10, 17, 28 In a setting of cirrhosis with ascites, bacterial translocation results from enteric bacterial overload, deranged intestinal permeability, and probably also impaired intestinal immunity, which is unable to eliminate the translocated

Imatinib chemical structure microorganisms.6, 16, 29 The detection of bacterial genome fragments but not of viable bacteria in the MLNs of our rats with preascitic cirrhosis indicates that the mechanisms leading to passage of enteric bacteria to the MLNs are also operative at the pre-ascitic stage of experimental cirrhosis. However, and in contrast to rats with ascites, a functional intestinal immune system is able to eradicate the accessing bacteria. Interestingly, in our study, bacterial CpG motifs, which are immunologically active components of bacterial DNA,30 were able to elicit an inflammatory response in the MLNs with expansion of activated mononuclear cells and production

of proinflammatory cytokines. Remarkably, the immune system at the MLNs was able to maintain the inflammatory response to bacterial DNA 上海皓元医药股份有限公司 fragments at the local level. This was revealed by a lack of correlation between the expansion of activated immune cells at the systemic level and the presence of bacterial DNA at the MLNs or bowel decontamination with antibiotics. We sought to detect systemic inflammation in rats with CCl4 cirrhosis, given that it is the most widely used and clearly characterized toxin-based experimental model of cirrhosis. This model has been shown to effectively mimic many of the features of human cirrhosis associated with toxic damage.