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Altered serum transforming growth factor-beta1 and monocyte chemoattractant protein-1 levels in obstructive jaundice
Shyr-Ming Sheen-Chen1, Hock-Liew Eng, Kuo-Sheng Hung
1Department of Surgery, College of Medicine, Chang Gung University, Chang Gung Memorial Hospital, Kaohsiung, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung Hsien, Taiwan. smsheen@yahoo.com
Impaired immune function has long been documented in patients with obstructive jaundice, and those with jaundice due to extrahepatic biliary obstruction still experience a high rate of postoperative complications and death. Transforming growth factor-beta1 (TGFbeta1) appears to be an important regulator of both normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1 (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites. We hypothesize that obstructive jaundice may alter serum TGFbeta1 and MCP-1 expressions in the rat and that oral bile acid or glutamine (or both) can restore the altered serum TGFbeta1 and MCP-1 expression in rats with obstructive jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (n = 10 in each group). Group 1 underwent a sham operation with oral normal saline administration. Group 2 underwent common bile duct ligation (CBDL) with oral normal saline administration. Group 3 underwent CBDL with oral bile acid replacement. Group 4 underwent CBDL with oral glutamine administration. Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood samples were collected. Serum was obtained after centrifugation for measurement of TGFbeta1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum TGFbeta1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral glutamine administration prevented this elevation, but oral bile acid replacement did not. The serum MCP-1 level showed similar changes. After 3 days of obstructive jaundice, the TGFbeta1 and MCP-1 levels were altered in the rat. Oral glutamine administration, not oral bile acid replacement, was able to prevent these alterations.
Impaired immune function has long been documented in patients with obstructive jaundice, and those with jaundice due to extrahepatic biliary obstruction still experience a high rate of postoperative complications and death. Transforming growth factor-beta1 (TGFbeta1) appears to be an important regulator of both normal and pathologic conditions in the liver. Monocyte chemoattractant protein-1 (MCP-1) is an important mediator of monocyte recruitment to inflammatory sites. We hypothesize that obstructive jaundice may alter serum TGFbeta1 and MCP-1 expressions in the rat and that oral bile acid or glutamine (or both) can restore the altered serum TGFbeta1 and MCP-1 expression in rats with obstructive jaundice. Male Sprague-Dawley rats weighing 250 to 300 g were randomized to four groups (n = 10 in each group). Group 1 underwent a sham operation with oral normal saline administration. Group 2 underwent common bile duct ligation (CBDL) with oral normal saline administration. Group 3 underwent CBDL with oral bile acid replacement. Group 4 underwent CBDL with oral glutamine administration. Animals were sacrificed after 3 days (n = 5) and 7 days (n = 5), and blood samples were collected. Serum was obtained after centrifugation for measurement of TGFbeta1 and MCP-1 levels by an enzyme-linked immunosorbent assay. The serum TGFbeta1 level was significantly elevated (p = 0.006) 3 days after CBDL. Oral glutamine administration prevented this elevation, but oral bile acid replacement did not. The serum MCP-1 level showed similar changes. After 3 days of obstructive jaundice, the TGFbeta1 and MCP-1 levels were altered in the rat. Oral glutamine administration, not oral bile acid replacement, was able to prevent these alterations.
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