Liver injury in acute pancreatitis and mitigation by continuous arterial infusion of an antibiotic via the superior mesenteric artery.
Macrophage-derived inflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha), have been shown to play a central role in aggravation of acute pancreatitis (AP), but little is known about their roles in liver injury. We investigated the pathogenesis of the liver injury in AP and assessed the efficacy of arterial infusion of an antibiotic via the superior mesenteric artery (SMA). Infusion of saline (group A) or imipenem (group B) was started 6 hours after induction of AP in dogs by intraductal administration of autologous gallbladder bile. The survival rate in group B was significantly improved compared with group A. Serum alanine aminotransferase levels in peripheral blood and endotoxin levels in portal vein blood were both significantly higher at 18 hours in group A than in group B. When hepatocytes and Kupffer cells were isolated at 18 hours and cultured for 24 hours thereafter, there was significant exacerbation of the hepatocyte injury and significantly greater production of TNF-alpha in the coculture of hepatocytes and Kupffer cells in group A, indicating that the Kupffer cells had been activated. By contrast, both of these manifestations were significantly mitigated in group B. These findings suggest that TNF-alpha secreted by endotoxin-activated Kupffer cells contributes to liver injury in AP, and that SMA infusion of an antibiotic mitigates the liver injury by controlling endotoxin translocation.
Miyahara
S
S
First Department of Surgery, Mie University School of Medicine, Tsu, Japan.
Isaji
S
S
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D004285:Dogs; D004731:Endotoxins / Q000097:blood; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D015378:Imipenem / Q000008:administration & dosage; D066298:In Vitro Techniques; D007261:Infusions, Intra-Arterial; D007728:Kupffer Cells / Q000187:drug effects / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D008297:Male; D017538:Mesenteric Artery, Superior; D010195:Pancreatitis / Q000188:drug therapy* / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000900:Anti-Bacterial Agents; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D015378:Imipenem; D007770:L-Lactate Dehydrogenase; D000410:Alanine Transaminase