Ursodeoxycholic acid inhibits eosinophil degranulation in patients with primary biliary cirrhosis

Eosinophilia is a distinctive feature of primary biliary cirrhosis (PBC), e specially in its early stages, Intriguingly, treatment with ursodeoxycholic acid (UDCA) ameliorates eosinophilia as well as liver tests in patients wi th PBC, It remains unknown, however, whether eosinophils in PBC patients ar e functionally activated and whether UDCA inhibits eosinophil activation. I n the present study, we systematically examined eosinophil dynamics in the blood and liver in patients with stage I to II PBC before and after UDCA tr eatment. We determined serum concentrations of eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]) by radi oimmunoassay and quantitated eosinophil degranulation using computer-assist ed morphometry after MBP immunohistochemistry Before UDCA treatment, patien ts with PBC (n = 25) showed significantly higher circulating eosinophil cou nts (P <.05) and serum concentrations of MBP (P <.0005) and EDN (P <.02) co mpared with patients with chronic viral hepatitis (n = 22), autoimmune hepa titis (n = 10), and obstructive jaundice (n = 12), Four-week UDCA treatment significantly reduced blood eosinophil counts (P <.0001) and serum MBP (P <.0001) and EDN (P <.0001) levels in PBC pa tie n ts, MB P immunohistochemi stry and computer-assisted quantitative morphometry showed infiltration and degranulation of eosinophils in the portal tract in patients with PBC and significant reductions in the number of sites and the area occupied by extr acellular MBP deposits after UDCA treatment for 2 years (P <.02) but not in placebo-treated patients. Our results suggest that eosinophils in patients with PBC are not only increased in number, but also release granule protei ns, and that UDCA treatment inhibits this eosinophil activation/degranulati on.