title: Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography.
abstract: This prospective observational study investigated monocyte cytokine responses to lipopolysaccharide (LPS) in patients with obstructive jaundice (OJ) before and after endoscopic biliary drainage. Dendritic cell (DC) subsets and their expression of co-stimulatory molecules were also studied. Forty patients with OJ and ten non-jaundiced patients with normal gastroscopy findings were recruited. Ten healthy volunteers provided control blood samples for immunological assays. Patients with OJ had blood and duodenal mucosa sampled at the time of endoscopic retrograde cholangiopancreatography (ERCP) and further blood sampled during the recovery phase. Monocyte cytokine responses to LPS, DC subsets and co-stimulatory molecule expression were compared with controls. Duodenal morphology and occludin expression were also assessed. Monocytes obtained before ERCP from jaundiced patients demonstrated reduced cytokine responses to endotoxin compared with controls (IL-1β: 2678 compared with 4631 pg/ml, P=0.04 and IL-6: 3442 compared with 6157 pg/ml, P=0.002). Monocytes from patients with malignancy had poorer responses to endotoxin than from those with benign OJ (IL-1β: 2025 compared with 3332 pg/ml, P=0.001). After ERCP, the secretion of inflammatory cytokines by monocytes obtained from jaundiced patients increased (IL-1β: 2150 compared with 2520 pg/ml, P=0.03 and IL-6: 2488 compared with 3250 pg/ml, P=0.01). Occludin expression (85 compared with 95%, P=0.004) and mean duodenal villus height (334 compared with 404 μm, P=0.03) were lower in jaundiced patients. Before biliary drainage, patients with OJ had a higher percentage of myeloid dendritic cells (mDCs) and greater mDC expression of CD40 (P=0.04) and CD86 (P=0.04). Monocytes from patients with OJ had lower proinflammatory cytokine secretion in response to LPS, an effect reversed following biliary drainage.
authors.affiliation: National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, U.K.
authors.forename: Abeed H
authors.initials: AH
authors.lastname: Chowdhury
authors.affiliation: School of Life Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, U.K.
authors.forename: Miguel
authors.initials: M
authors.lastname: Camara
authors.affiliation: School of Life Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, U.K.
authors.forename: Luisa
authors.initials: L
authors.lastname: Martinez-Pomares
authors.affiliation: National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, U.K.
authors.forename: Abed M
authors.initials: AM
authors.lastname: Zaitoun
authors.affiliation: National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, U.K.
authors.forename: Oleg
authors.initials: O
authors.lastname: Eremin
authors.affiliation: National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, U.K.
authors.forename: Guruprasad P
authors.initials: GP
authors.lastname: Aithal
authors.affiliation: National Institute for Health Research Nottingham Digestive Diseases Biomedical Research Unit, Nottingham University Hospitals NHS Trust and University of Nottingham, Queen's Medical Centre, Nottingham NG7 2UH, U.K. dileep.lobo@nottingham.ac.uk.
authors.forename: Dileep N
authors.initials: DN
authors.lastname: Lobo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002760:Cholangiopancreatography, Endoscopic Retrograde; D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D041781:Jaundice, Obstructive / Q000000981:diagnostic imaging / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6
keywords: cytokines; dendritic cells; duodenal morphology; endotoxin tolerance; immune dysfunction; obstructive jaundice