Immune dysfunction in patients with obstructive jaundice before and after endoscopic retrograde cholangiopancreatography.

Abeed H Chowdhury,Abed M Zaitoun,Miguel Camara,Dileep N Lobo,Oleg Eremin,Guruprasad P Aithal,Luisa Martinez-Pomares

doi:10.1042/cs20160326

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.

Highlights

Patients with obstructive jaundice (OJ) are at a higher risk of perioperative complications than those without jaundice [1,2,3]
Serum bilirubin concentrations were significantly higher in patients with malignant OJ prior to drainage, there was no significant difference between groups after drainage
This study has demonstrated that OJ is associated with diminished monocyte proinflammatory cytokine secretion following exposure to LPS in vitro, when compared with healthy controls

Summary

Introduction

Patients with obstructive jaundice (OJ) are at a higher risk of perioperative complications than those without jaundice [1,2,3]. The underlying mechanisms for this elevated risk are not fully understood, evidence suggests that OJ may allow translocation of bacteria or bacterial products into the portal and, subsequently, systemic circulations which might result in chronic activation of immune cells in response to endotoxin exposure. The evidence supporting this hypothesis has come mainly from animal models as it is difficult to sample portal blood or lymphoid tissue in humans [6,7]. This paper has been published in abstract form: British Journal of Surgery 2014; 101 (S4): 47–48 (Abstract No.: O167)

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