Poor outcome in bacterial peritonitis is associated with dysregulated microRNAs and an increased inflammatory response

Abstract

Peritonitis is a common cause of surgical sepsis. The failure of the host to mount an appropriate immune response contributes to persistence of the infection. We investigated the role microRNAs may play in this failed immune response. Klebsiella pneumoniae was injected intraperitoneally in mice. Weight loss was used to predict clinical outcome. Peritoneal exudate cells (PECs) and supernatant were collected. RNA from PECs was run on screening microRNA array cards to determine gene expression, and validated by single assay analysis. Cytokine levels in supernatant were assayed by enzyme-linked immunosorbent assay. Despite similar bacterial levels, PEC counts were higher in the predicted death group. The predicted deaths had higher levels of proinflammatory tumor necrosis factor-α/IL-6 and significantly lower levels of interleukin-10. MiR-221 was up-regulated in both the predicted death and predicted survivor groups. Five miRNAs were up-regulated in the predicted survivor group compared with normal controls. Higher PEC counts and proinflammatory cytokines in the predicted death group indicates an exaggerated inflammatory response, with lower IL-10 levels despite similar bacterial counts. There were two dysregulated miRNAs with transcriptional targets that may explain our results. A more balanced immune response with an appropriate counter inflammatory response may be important for improving survival.