Alteration of intestinal epithelial function by intraepithelial lymphocyte homing.

BACKGROUND: Intimate cross-talk may take place between intestinal epithelial cells and intraepithelial lymphocytes (IEL). The purpose of this study was to analyze the influence of lymphocyte migration into the epithelium on epithelial function, using an in vitro "IEL homing" model. METHODS: Molecular expression on epithelial cells was analyzed by flow cytometry. The barrier function of the epithelial monolayer was assessed by transepithelial electrical resistance. Cytokine production was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) IEL homing into the epithelia induced significant phenotypic changes in epithelial cells; upregulation of MHC class I, and II, intercellular adhesion molecule (ICAM)-1, and CD44. IEL-derived interferon-gamma (IFN-gamma) could partially account for this alteration, as a neutralizing antibody (Ab) against IFN-gamma inhibited the upregulation of these molecules, except for CD44. (2) A marked fall in transepithelial electrical resistance was observed 4 h after IEL homing started, and Ab against IFN-gamma slightly inhibited this fall in resistance. (3) The production of interleukin (IL)-8 and IFN-gamma inducible protein-10 (IP-10), but not transforming growth factor (TGF)-beta1 or tumor necrosis factor (TNF)-alpha, in the epithelial monolayer was markedly induced after IEL homing in a basolaterally polarized fashion. IEL-conditioned media also induced the production of these cytokines in epithelial cells, thus suggesting that IEL-derived soluble factor(s) induce epithelial chemokine production. CONCLUSIONS: Under inflammatory conditions, IEL obviously interact with epithelial cells and upregulate adhesion molecules, alter barrier function, and enhance chemokine production. Because such alterations may increase epithelial permeability to luminal antigens or accelerate the migration of other inflammatory cells, our results suggest that IEL have a critical role in mucosal immunity.

Efficacy of endoscopic nasobiliary drainage for the prevention of pancreatitis after papillary balloon dilatation: a pilot study.

OBJECTIVE: Endoscopic papillary balloon dilatation (EPBD) has been reported to increase the risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (4%-11%). Based on the hypothesis that performing endoscopic nasobiliary drainage (ENBD) could prevent this complication, we performed EPBD combined with ENBD (EPBD/ENBD) and analyzed the risk of pancreatitis. METHODS: Thirty-four patients underwent EPBD followed by ENBD for common bile duct stone(s). Serum amylase levels the following morning and incidence of pancreatitis were compared with those previously reported and with complications of simple diagnostic ERCP performed in our institution. RESULTS: After EPBD/ENBD, amylase levels the following morning were 214.5 +/- 152.9 U/L, and no cases developed pancreatitis or hyperamylasemia (>3 times normal). These outcomes were favorable compared with previous EPBD reports. Furthermore, despite the stress of EPBD/ENBD after ERCP, these outcomes were better, even compared with simple ERCP performed at our institution [amylase levels: 318.7 +/- 475.2 U/L; hyperamylasemia: 16.5% (P = 0.006); pancreatitis: 7.1%]. CONCLUSION: Although EPBD has been regarded as a risk factor for post-ERCP pancreatitis, our results suggest the possibility that application of ENBD after EPBD decreases the incidence of pancreatitis and should be studied further. We speculate that ENBD itself prevents pancreatic duct obstruction by residual stones or papillary edema.