title: Ursodeoxycholic acid inhibits eosinophil degranulation in patients with primary biliary cirrhosis.
abstract: Eosinophilia is a distinctive feature of primary biliary cirrhosis (PBC), especially in its early stages. Intriguingly, treatment with ursodeoxycholic acid (UDCA) ameliorates eosinophilia as well as liver tests in patients with PBC. It remains unknown, however, whether eosinophils in PBC patients are functionally activated and whether UDCA inhibits eosinophil activation. In 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 treatment. We determined serum concentrations of eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]) by radioimmunoassay and quantitated eosinophil degranulation using computer-assisted morphometry after MBP immunohistochemistry. Before UDCA treatment, patients with PBC (n = 25) showed significantly higher circulating eosinophil counts (P <. 05) and serum concentrations of MBP (P <.0005) and EDN (P <.02) compared with patients with chronic viral hepatitis (n = 22), autoimmune hepatitis (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 patients. MBP immunohistochemistry 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 extracellular 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 proteins, and that UDCA treatment inhibits this eosinophil activation/degranulation.
authors.affiliation: Department of Immunology, Mayo Clinic and Mayo Foundation, Rochester, MN, USA. Yamazaki.Kiyoshi@mayo.edu
authors.forename: K
authors.initials: K
authors.lastname: Yamazaki
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Nakamura
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: K D
authors.initials: KD
authors.lastname: Lindor
authors.forename: K P
authors.initials: KP
authors.lastname: Batts
authors.forename: J E
authors.initials: JE
authors.lastname: Tarara
authors.forename: G M
authors.initials: GM
authors.lastname: Kephart
authors.forename: H
authors.initials: H
authors.lastname: Kita
authors.forename: G J
authors.initials: GJ
authors.lastname: Gleich
mesh_terms: D001798:Blood Proteins / Q000032:analysis; D015550:Cell Degranulation / Q000187:drug effects*; D002779:Cholestasis / Q000097:blood; D047091:Eosinophil Granule Proteins; D047208:Eosinophil-Derived Neurotoxin; D004804:Eosinophils / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure*; D005260:Female; D019693:Hepatitis, Autoimmune / Q000097:blood; D006525:Hepatitis, Viral, Human / Q000097:blood; D006801:Humans; D007150:Immunohistochemistry; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology*; D008105:Liver Cirrhosis, Biliary / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D010919:Placebos; D011506:Proteins / Q000032:analysis; D011863:Radioimmunoassay; D012260:Ribonucleases; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D010919:Placebos; D011506:Proteins; D014580:Ursodeoxycholic Acid; D047208:Eosinophil-Derived Neurotoxin; D012260:Ribonucleases