Ascites of rat experimental model of severe acute pancreatitis induces lung injury

The molecular mechanisms that lead from acute pancreatitis (AP) to multiple organ failure remain to be clarified. We previously reported that ascitic fluids from a rat model of severe acute pancreatitis (pancreatitis-associat ed ascitic fluids, PAAF) transcriptionally activated endothelial cells and leukocytes in vitro. To clarify the role of ascitic fluids on the developme nt of multiple organ failure in AP, we examined the effects of PAAF on the prognosis and immunohistologic findings in cerulein pancreatitis, an experi mental model of mild pancreatitis in vivo. Intraperitoneal injection of PAA F decreased the survival rates in a dose-dependent manner. Histologically, destruction of vessels, alveolar septal thickening, interstitial hypertroph y, and infiltration of inflammatory cells were prominent in the lung of PAA F-injected rats. Transcription factor, nuclear factor kappaB (NF-kappaB) wa s activated and the mRNA levels of tumor necrosis factor-alpha and interleu kin-lp were increased in the lung of the PAAF-injected rats. The permeabili ty index assessed by Evans blue assay and the lung myeloperoxidase activity levels were significantly higher in the PAAF-injected rats than in control s. Inhibition of NF-kappaB ameliorated the histologic findings and improved the survival rates. Our results suggest that PAAF play a role in the patho genesis of lung injury in severe AP, at least in part through the activatio n of NF-kappaB.