Cytokines and the progression of liver damage in experimental bile duct ligation

1. Cytokines are soluble factors whose action has been documented in physio logical and pathological conditions. Some may be involved in the pathogenes is of cholestasis, whether of acute or chronic origin, 2. The aim of the present study was to evaluate the influence of epidermal growth factor (EGF), transforming growth factor (TGF)-beta(1), interleukin (IL)-6 and tumour necrosis factor (TNF) on cholestasis. Findings from Sprag ue-Dawley rats submitted to bile duct ligation for 1-28 days were compared with those from controls, which underwent laparotomy but not bile duct liga tion, 3, Biochemical and morphological findings confirmed that the experimental p rocedure was successful, At the end of each follow-up period, the hepatic l evels of the cytokines were determined and compared with liver histology fi ndings. 4, The four cytokines studied showed different patterns of activation: hepa tic levels of EGF, higher in the experimental than the control group, were comparable with the proliferative picture. The TGF-beta(1) pattern was corr elated with data of periportal, perivenular and perineoductular fibrosis, c onfirming that this cytokine has a role in mediating the synthesis of matri x proteins, A fluctuating, phasic pattern was found for TNF in the experime ntal group, with high values on day 0, a decrease on the first and second p ostoperative days and then two peaks on days 8 and 14, Finally, immediately after surgical manipulation, high levels of IL-6 were found in the experim ental group, followed by a decrease in levels until zero values were obtain ed, 5. This suggests that the obstructive condition produces several cytokine r esponses, each of which contributes to determine the cholestatic condition.