engleski

Cholestasis-induced changes of cytotoxicity and comparison of laparoscopic and open cholecystectomy

INTRODUCTION: Biliary obstruction and surgery induces significant immune dysfunctions, which in patients subjected to surgery may be responsible for serious peri-operative complications and high mortality rate. The effects might be linked with the liver injury induced by cholestasis, as well as by stress of operation, since both conditions induce the disarrangements of innate and specific immunity. In an attempt to elucidate both possibilities in this study: 1) we compared the immune status of peripheral blood in patients subjected to laparoscopic (LC) and open (OC) cholecystectomy (LC), correlating the data with intensity of their cholestasis and inflammatory conditions, and 2) investigated the phenotypic characteristics and cytotoxicity of intrahepatic and splenic mononuclear lymphatic cells (MNLC) against NK and LAK-sensitive cell lines in mice subjected to common bile duct ligation. METHODS: Analyses were done in 44 patients with gallstones, subjected to LC or OC, whose blood samples were driven 1 day before and on the first day after surgery. Flow cytometry was used for simultaneous detection of intracellular (perforin) and cell surface antigens on T and NK cells. In mice, the cytotoxicity on freshly isolated hepatic and splenic MNLC was tested against YAC-1, P815, and against the syngeneic thymocytes. Tests were made by the use of flow cytometry and PKH-26 Red 2h cytotoxicity assay. RESULTS: The data showed that in humans OC significantly decreased the percentage of CD56+ cells and increased the percentage of CD19+ cells, while LC decreased the percentage of CD8+P+ T cells, but increased the proportion of CD16+P+ and CD56+P+ NK cells, probably owing to stimulation by pneumoperitoneum. However, in both groups the effects were clearly dependent on the intensity of preoperative cholestasis and serum levels of C-reactive proteins, which significantly increased the percentage of CD4+P+ cells in the peripheral blood (r=0. 51 and 0, 62 ; respectively ; p<0.000). Moreover, cholestasis in mice was followed by hepatic accumulation of NKT cells and increased cytotoxicity against all tested cells lines. CONCLUSION: The data point to jaundice, as an important inducer of the cytotoxic CD4+ T cells and NKT cells, which might belong to regulatory clones of cells, activated by injury in the liver.

holestasis; cytotoxicity; laparoscopic and open cholecistectomy

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