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 an imal models it has been postulated that cholestasis affects systemic polymo rphonuclear 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 producti on of oxygen-derived free radicals in chronic cholestatic liver diseases. METHODOLOGY: The following groups were included in the study: 27 primary bi liary cirrhosis (PBC) patients, 12 primary sclerosing cholangitis (PSC) pat ients, and 3 control groups (29 healthy subjects, 19 patients with HCV-rela ted cirrhosis and 23 ulcerative colitis (UC) patients). Peripheral neutroph ils were isolated from heparinized blood samples and PMNL activity was meas ured by free radical production, using a chemiluminometer, after stimulatio n with fMLP, PMA and Zymosan. The effect of liver disease severity and degr ee of cholestasis on PMNL function was also evaluated. RESULTS: Both PBC and PSC patients exhibited a normal PMNL activity compare d to healthy subjects after the three stimuli used. In PBC patients only (b ut not in PSC patients), the histological stage of the disease seems to pos itively influence ROS production. Stage TV PBC patients showed a significan tly higher PMNL activity compared to HCV-related cirrhotic patients. PSC pa tients failed to show any difference according to the association with UC. CONCLUSIONS: The increased susceptibility to bacterial infections in patien ts with chronic cholestatic liver disease is not related to an impaired PMN L activity. However, our findings may support the influence of biohumoral f actors (cytokines?) on PMNL activation.