The Expressions Of IL-6, NF-κB And ICAM-1 In Intestinal Mucosa Of Patients With Obstructive Jaundice

Objective: Obstructive jaundice may compromise the function of the intestinal barrier. The bacteria and endotoxins in the gut would translocate to portal and systemic circulation through the injured intestinal mucosa, which result in a series of complications, such as endotoxaemia, renal failure even death. By now, the mechanism of the intestinal mucosa damages has not been literally clarified. The increased intestinal bacteria and endotoxins in the obstructive jaundice would induce the immune response and release many inflammatory mediators and cytokines. Interleukin-6 (IL-6) secreted by immunocytes and lots of interrelated cells is a vital cytokine, which plays an extensive role of regulating immunity. IL-6 could stimulate the proliferation and differentiation of B cells, and induce B cells to excrete antibodies. Meanwhile, as a hepatocyte-stimulating factor, IL-6 could induce the synthesis of the acute phase reactive protein and mediate the different immune and inflammatory reaction through activating T lymphocyte. Nuclear factor of kappa B (NF-κB) was firstly found by Sen from the extract of B lymphocyte in 1986. NF-κB usually combines with its inhibitive protein IκB and exists in the cytoplasm. NF-κB could be activated by many factors, and mediate many genes expressions, such as immunologic reaction, embryogenesis, apoptosis, tumor genesis, metastasis, physiologic reaction and pathologic reaction. NF-κB is a significant transcription factor and can specially combine with many cytogene promoter or enhancer sequences to promote transcription and expression. NF-κB is closely correlated with inflammatory reaction, immune response, cell proliferation, inversion, apoptosis and so on. Intercellular adhesion molecule-1 (ICAM-1) is a kind of transmembrane glycoprotein, which can mediate the adhesive attraction of cell and cell, cell and extracelluar matrix. ICAM-1 has many biological functions, and plays an important effect, such as mediating cell adhesion, the homing of lymphocyte, participating inflammatory and immune response. ICAM-1 usually no expresses or expresses little in normal intestinal mucosa. When stimulated by endotoxin and inflammatory cytokines, such as IL-1, TNF-α, ICAM-1 expresses in a lot of cells.The aims of this study were to observe the changes in intestinal morphology and ultrastructure of patients with obstructive jaundice and to analyze objectively the expressions of IL-6, NF-κB, ICAM-1 in intestinal mucosa of patients with obstructive jaundice in order to clarify the relationship between the expression of IL-6, NF-κB, ICAM-1 and the intestinal mucosa damages.Methods: Fifteen patients with obstructive jaundice who accepted ERCP in the department of Gastroenterology in The Second Hospital of Hebei Medical University from Jun 2007 to Nov 2007 were collected. Among them, 9 patients were suffered from the bile duct stones and 6 patients with periampullary carcinoma. Fifteen patients without any sign of jaundice or duodenal inflammation were collected as control. All patients underwent an ERCP, biopsies were obtained from the second part of the duodenum distal to the ampulla of Vater. All patients were clamped 3 biopsies. One biopsy was fixed by 4% glutaraldehyde, and electron microscopy was performed to observe the ultrastructural changes. Two biopsies were fixed by 10% formal and embedded in paraffin wax, then the sections measuring 4μm in thickness were cut and stained with haematoxylin and eosin. The changes of the intestinal mucosa were observed under light microscopy. In addition, using immunohistochemical method assayed the intestinal mucosa of the jaundiced patients and control to observe the expressions of IL-6, NF-κB and ICAM-1. The difference of expression was analyzed by t test to identify if there was statistic significance or not.Results: The sections were examined histologically using light microscopy. In control, the intestinal villi and enterocytes arrayed neatly and the heights of villi were consistent. In the jaundiced patients, the intestinal villi arrayed disorderly and were shorter or absent compared with control. The interval of villi was wider. Necrosis in the enterocytes and glands could be observed. Under electron microscopy, the microvilli were thick and the junctional complexes were integrity in control. In the jaundiced patients, electron microscopy revealed that the junctional complexes were integrity, but the microvilli were loose, the enterocytes became flat, the mitochondria swelled and the cristae of mitochondria collapsed, even the mitochondria vacuolated. In addition, it could be seen that there were several bacteria attached to the mucosa surface. For the result of immunohistochemistry, the positive products of IL-6 and NF-κB were localized in the nucleus and cytoplasm of cells and the positives cells were inflammatory cell, vascular endothelial cell and epithelial cell. The positive product of ICAM-1 was mainly localized at the cytoplasm of cells and the positives cells were inflammatory cell and gland cell. The positive expressions of IL-6, NF-κB and ICAM-1 in the jaundiced patients were higher than that of control (P<0.05), but there was no significant difference between the jaundiced patients caused by the stones of bile duct and the jaundiced patients by periampullary carcinoma (P>0.05).Conclusions: The intestinal mucosa of patients with obstructive jaundice is injured;The expressions of IL-6, NF-κB and ICAM-1 increase, which indicate that the mechanism of the intestinal mucosa damages is related to the IL-6, NF-κB and ICAM-1 disturbance in patients with obstructive jaundice.