Ce in the IL-6 level could be due to production by e.g.circulating monocytes. This finding was similar to what previously was found in a model of ALI in association with acute ischemic kidney injury [17]. As with IL-6, TNF-a represents a major determinant of the systemic progression and end-organ damage such as acute lung injury in acute pancreatitis [18]. In this study, a significant rise in the acute phase plasma TNF-a level in BPD group was observed at 24 h Indolactam V site compared to the sham operated group. Although utilizing a highly sensitive assay, the CVs at TNF-a levels below 5 pg/ml were relatively high and the low, although significant rise at the early 1 h was not considered biologically relevant. The severity of pancreatitis and pancreatitis-associated ALI relates to the balance between pro-inflammatory and antiinflammatory mediators. IL-10 is an anti-inflammatory cytokine that inhibits the release of pro-inflammatory cytokines from macrophages. Previous studies have shown a role of IL-10 in reducing the severity of acute pancreatitis and ALI [19,20]. The inflammatory response in the pancreas and the lungs was studied by quantifying the levels of the main chemoattractant proteins for neutrophil (CXCL1) and macrophages (CCL2). The increased levels of the chemoattractants in both tissues were further investigated by analyzing the recruitment of bothEnrichment of CD68+ Lung CellsEnrichment of CD68+ Lung CellsFigure 6. Changes in lung macrophage SC 1 web sub-populations during acute pancreatitis. Single cell preparations of the right lung were evaluated by flow cytometry. Dot plots from one representative experiment of sham control (A) and 24 
h post pancreatitis induction (B) showing the gating strategy. Significant modulations in the percentage of R1 (C) and R2 (D) gated populations following acute pancreatitis compared to sham operated animals. Representative profiles of CD68 and F4/80 expressing cells in the R1 population of sham (D) and ligated (E) mice after 24 h are shown. A significant enrichment in the total number of R1 gated CD68+ F4/802 cells in the right lung 9 h (F) and 24 h (G) after pancreatitis induction compared to sham controls. CD68+ cells were increased significantly in the immunohistochemical staining of the lung sections in the acute pancreatitis compared to sham at 9, 24 and 48 h. , n = 8 per group. *P,0.05, **P,0.01, ***P,0.001 versus control, by two-tailed Student t-test. doi:10.1371/journal.pone.0042654.gneutrophils and 
macrophages into pancreatic and lung tissue. The recruitment of neutrophils and macrophages in the pancreas followed the increased level of the corresponding chemoattractant. This was also noted in the lungs for neutrophils, but not for F4/80 positive macrophages. The findings are consistent with a previous study, in which F4/80 was used as a marker for detecting macrophages [21]. The CC chemokines, such as CCL2, macrophage inflammatory protein (MIP)-1a and RANTES are believed to primarily activate and recruit monocytes, whereas the CXC chemokines, such as CXCL1, preferentially tend to recruit neutrophils [22]. The CXCL1 increased levels in the pancreas and lungs in animals with acute pancreatitis compared to the sham operated group were not associated with a significant difference in the plasma levels between them. This finding along with the difference of the CXCL1 levels in the pancreas and lungs (almost four times less in the pancreas), indicate a local response in the lungs secreting CXCL1. Considering th.Ce in the IL-6 level could be due to production by e.g.circulating monocytes. This finding was similar to what previously was found in a model of ALI in association with acute ischemic kidney injury [17]. As with IL-6, TNF-a represents a major determinant of the systemic progression and end-organ damage such as acute lung injury in acute pancreatitis [18]. In this study, a significant rise in the acute phase plasma TNF-a level in BPD group was observed at 24 h compared to the sham operated group. Although utilizing a highly sensitive assay, the CVs at TNF-a levels below 5 pg/ml were relatively high and the low, although significant rise at the early 1 h was not considered biologically relevant. The severity of pancreatitis and pancreatitis-associated ALI relates to the balance between pro-inflammatory and antiinflammatory mediators. IL-10 is an anti-inflammatory cytokine that inhibits the release of pro-inflammatory cytokines from macrophages. Previous studies have shown a role of IL-10 in reducing the severity of acute pancreatitis and ALI [19,20]. The inflammatory response in the pancreas and the lungs was studied by quantifying the levels of the main chemoattractant proteins for neutrophil (CXCL1) and macrophages (CCL2). The increased levels of the chemoattractants in both tissues were further investigated by analyzing the recruitment of bothEnrichment of CD68+ Lung CellsEnrichment of CD68+ Lung CellsFigure 6. Changes in lung macrophage sub-populations during acute pancreatitis. Single cell preparations of the right lung were evaluated by flow cytometry. Dot plots from one representative experiment of sham control (A) and 24 h post pancreatitis induction (B) showing the gating strategy. Significant modulations in the percentage of R1 (C) and R2 (D) gated populations following acute pancreatitis compared to sham operated animals. Representative profiles of CD68 and F4/80 expressing cells in the R1 population of sham (D) and ligated (E) mice after 24 h are shown. A significant enrichment in the total number of R1 gated CD68+ F4/802 cells in the right lung 9 h (F) and 24 h (G) after pancreatitis induction compared to sham controls. CD68+ cells were increased significantly in the immunohistochemical staining of the lung sections in the acute pancreatitis compared to sham at 9, 24 and 48 h. , n = 8 per group. *P,0.05, **P,0.01, ***P,0.001 versus control, by two-tailed Student t-test. doi:10.1371/journal.pone.0042654.gneutrophils and macrophages into pancreatic and lung tissue. The recruitment of neutrophils and macrophages in the pancreas followed the increased level of the corresponding chemoattractant. This was also noted in the lungs for neutrophils, but not for F4/80 positive macrophages. The findings are consistent with a previous study, in which F4/80 was used as a marker for detecting macrophages [21]. The CC chemokines, such as CCL2, macrophage inflammatory protein (MIP)-1a and RANTES are believed to primarily activate and recruit monocytes, whereas the CXC chemokines, such as CXCL1, preferentially tend to recruit neutrophils [22]. The CXCL1 increased levels in the pancreas and lungs in animals with acute pancreatitis compared to the sham operated group were not associated with a significant difference in the plasma levels between them. This finding along with the difference of the CXCL1 levels in the pancreas and lungs (almost four times less in the pancreas), indicate a local response in the lungs secreting CXCL1. Considering th.