부산대학교 도서관

Liver disease is one of the leading causes of death worldwide (1). Patients with cirrhosis display an increased predisposition to and mortality from infection due to multimodal defects in the innate immune system (2-4); however, the causative mechanism has remained elusive. We present evidence that the cyclooxygenase (COX)-derived eicosanoid prostaglandin [E.sub.2] (PG[E.sub.2]) drives cirrhosis-associated immunosuppression. We observed elevated circulating concentrations (more than seven times as high as in healthy volunteers) of PG[E.sub.2] in patients with acute decompensation of cirrhosis. Plasma from these and patients with end-stage liver disease (ESLD) suppressed macrophage proinflammatory cytokine secretion and bacterial killing in vitro in a PG[E.sub.2]-dependent manner via the prostanoid type E receptor-2 (EP2), effects not seen with plasma from patients with stable cirrhosis (Child-Pugh score grade A). Albumin, which reduces PG[E.sub.2] bioavailability, was decreased in the serum of patients with acute decompensation or ESLD (
The prevalence of liver disease is predicted to rise dramatically as a consequence of the global trends of obesity, higher alcohol consumption and rising hepatitis C virus transmission (1). Bacterial [...]