Protein expression mimicked, again, gene expression and is represented in the corresponding blots along Fig. 5 (data on protein band densitometry is provided in Supporting Information Fig. 1). As a control, IL-10 levels were measured in all cell supernatants, to evaluate free IL-10 available for its receptor to signal down. Levels were almost undetectable for the first set of cultured cells and significantly increased in the second set (data not shown). The current study shows an IL-10–mediated HO-1–induced anti-inflammatory mechanism present in patients with cirrhosis receiving norfloxacin as secondary Ensartinib mw prophylaxis for

SBP. Although the association between norfloxacin and this mechanism does not imply causality and would require Selleck CH5424802 further molecular studies, it directly associates norfloxacin with cell-modulating events in these patients. Besides its known bactericidal effect on intestinal gram-negative bacterial flora, norfloxacin has been shown to induce several immunological effects at the cellular level, decreasing proinflammatory cytokines, controlling oxidative burst, and restoring the apoptotic rate in compromised PMN cells.10 However, molecular control of the proinflammatory response remained to

be underlined in this setting. To validate our results, we compared patients with SID with a matched control group of patients with cirrhosis and ascites who are not taking norfloxacin and also with patients who have SBP, as a control group with an overt infection. In our study, an initial screening of several anti-inflammatory mediators revealed IL-10 as a significantly increased cytokine 上海皓元医药股份有限公司 in patients with SID compared with patients with noninfected AF that positively correlated with serum norfloxacin levels. IL-10 signaling induces the expression of HO-1, a stress-inducible protein with anti-inflammatory activity, through a p38 mitogen-activated

protein kinase–dependent pathway.15, 16 Accordingly, we observed that HO-1 levels were also increased in patients with SID versus patients with noninfected AF and that significantly correlated with norfloxacin serum levels as well (Fig. 1). On the contrary, different proinflammatory mediators such as NF-κB, iNOS, and COX-2 showed a norfloxacin-dependent down-regulation in patients with SID compared with patients with noninfected AF and patients with SBP (Fig. 2). From this starting point, patients with SID were distributed into three subgroups according to intracellular norfloxacin range levels to further investigate the inflammatory balance dependency on norfloxacin concentration. LPS treatment significantly increased mRNA expression levels of all proinflammatory mediators in neutrophils from patients with noninfected AF to those present in SBP whereas increasing amounts of intracellular norfloxacin limited proinflammatory molecule levels to those observed in resting cells.