Oxygen-derived free radical production by peripheral blood neutrophils in chronic cholestatic liver diseases.

BACKGROUND/AIMS: Patients with chronic cholestasis, particularly those with associated cirrhosis, are susceptible to infectious complications. From animal models it has been postulated that cholestasis affects systemic polymorphonuclear leukocyte (PMNL) function by impeding chemotaxis, phagocytosis and superoxide release, which are necessary for an adequate immune response. The aim of this study was to evaluate neutrophil activity in the production of oxygen-derived free radicals in chronic cholestatic liver diseases. METHODOLOGY: The following groups were included in the study: 27 primary biliary cirrhosis (PBC) patients, 12 primary sclerosing cholangitis (PSC) patients, and 3 control groups (29 healthy subjects, 19 patients with HCV-related cirrhosis and 23 ulcerative colitis (UC) patients). Peripheral neutrophils were isolated from heparinized blood samples and PMNL activity was measured by free radical production, using a chemiluminometer, after stimulation with fMLP, PMA and Zymosan. The effect of liver disease severity and degree of cholestasis on PMNL function was also evaluated. RESULTS: Both PBC and PSC patients exhibited a normal PMNL activity compared to healthy subjects after the three stimuli used. In PBC patients only (but not in PSC patients), the histological stage of the disease seems to positively influence ROS production. Stage IV PBC patients showed a significantly higher PMNL activity compared to HCV-related cirrhotic patients. PSC patients failed to show any difference according to the association with UC. CONCLUSIONS: The increased susceptibility to bacterial infections in patients with chronic cholestatic liver disease is not related to an impaired PMNL activity. However, our findings may support the influence of biohumoral factors (cytokines?) on PMNL activation.