Biliary lactoferrin concentrations are increased in active inflammatory bowel disease: a factor in the pathogenesis of primary sclerosing cholangitis?

Abstract

1. One hypothesis for the link between inflammatory bowel disease and primary sclerosing cholangitis is that neutrophil activators, such as bacterial chemotactic peptides or neutrophil granule products themselves, pass from the inflamed colon to the liver via an enterohepatic circulation. However, there are no data on biliary concentrations of neutrophil granule products in patients with active and inactive inflammatory bowel disease.2. Gall bladder bile was obtained at laparotomy from 42 patients with ulcerative colitis and 21 patients with Crohn's disease. Biliary lactoferrin and myeloperoxidase concentrations were quantified by ELISA.3. In active ulcerative colitis, the mean lactoferrin concentration in gall bladder bile of 2.8+/-0.40 mg/l was higher than that seen after colectomy (1.2+/-0.11 mg/l; P<0.0001) or in patients with pouchitis (1.8+/-0.34 mg/l; P=0.06). In active Crohn's colitis, the mean lactoferrin concentration was 3.7+/-0.9 mg/l, compared with 1.1+/-0. 24 mg/l in the post-colectomy group (P<0.05) and 3.1+/-0.71 mg/l in those with active ileitis or ileocolitis. In contrast, biliary myeloperoxidase concentrations were low and comparable in all groups, with a mean concentration in the 42 patients with ulcerative colitis of 11.2+/-1.9 microgram/l.4. In contrast to myeloperoxidase, biliary lactoferrin concentrations are increased in active ulcerative colitis and Crohn's disease, and fall with colectomy and with disease remission. These findings indirectly support the hypothesis that bacterial chemotactic peptides (which induce selective degranulation of neutrophil secondary granules), and/or lactoferrin itself, undergo an enterohepatic circulation.