title: The augmented neutrophil respiratory burst in response to Escherichia coli is reduced in liver cirrhosis during infection.
abstract: Several functional abnormalities in phagocytes from patients with liver cirrhosis contribute to an increased risk of infection. An increased resting respiratory burst has been observed in neutrophils from cirrhotic patients. We investigated whether an infection in cirrhosis affects the respiratory burst capacity of neutrophils and monocytes in response to Escherichia coli. This study included 45 hospitalized patients with liver cirrhosis and clinical signs of infection, 39 patients with liver cirrhosis in the absence of infection and 29 healthy subjects. Respiratory burst, lipopolysaccharide-binding protein (LBP), and immunoglobulin (Ig)G-autoantibodies against oxidized low-density lipoproteins (ab-oxLDL) were measured. The fraction of neutrophils spontaneously producing reactive oxygen species (ROS) was elevated in liver cirrhosis (P < 0·01). The neutrophil resting burst increased with Child-Pugh stage (P = 0·02) and correlated with augmented ROS release in response to opsonized E. coli (P < 0·05). Although LBP was increased in patients with cirrhosis (P < 0·01), higher LBP levels correlated with a lower resting burst in neutrophils (r(s)  = -0·395; P < 0·01). In the presence of infection, the resting burst was unaltered. However, neutrophil ROS release in response to E. coli was reduced markedly (P = 0·01), and it decreased as serum C-reactive protein (CRP) concentration rose (r(s)  = -0·437; P < 0·01), indicating the development of a sepsis-like immune paralysis. A positive correlation between ab-oxLDL and ROS release was observed (P < 0·01). In conclusion, the respiratory burst increases with severity of liver cirrhosis but is restrained by increasing LBP levels. Augmented ROS release in response to E. coli is accompanied by elevated markers of oxidative damage and becomes exhausted in the presence of infection.
authors.affiliation: Division of Gastroenterology, Hepatology and Infectious Disease, Department of Internal Medicine II, Jena University Hospital, Jena, Germany. tony.bruns@med.uni-jena.de
authors.forename: T
authors.initials: T
authors.lastname: Bruns
authors.forename: J
authors.initials: J
authors.lastname: Peter
authors.forename: S
authors.initials: S
authors.lastname: Hagel
authors.forename: A
authors.initials: A
authors.lastname: Herrmann
authors.forename: A
authors.initials: A
authors.lastname: Stallmach
mesh_terms: D000209:Acute-Phase Proteins; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000942:Antigens, Bacterial / Q000276:immunology; D002352:Carrier Proteins / Q000097:blood; D002478:Cells, Cultured; D018450:Disease Progression; D004926:Escherichia coli / Q000276:immunology*; D005260:Female; D005355:Fibrosis / Q000150:complications / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D006801:Humans; D007239:Infections / Q000150:complications / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology; D008099:Liver / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D016897:Respiratory Burst / Q000276:immunology; D000099231:Lipopolysaccharide-Binding Protein
chemical_list: D000209:Acute-Phase Proteins; D000942:Antigens, Bacterial; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D017382:Reactive Oxygen Species; D000099231:Lipopolysaccharide-Binding Protein