TY - JOUR
T1 - Tumor necrosis factor-α and transforming growth factor-β reflect severity of liver damage in primary biliary cirrhosis
AU - Neuman, Manuela
AU - Angulo, Paul
AU - Malkiewicz, Izabella
AU - Jorgensen, Roberta
AU - Shear, Neil
AU - Dickson, E. Rolland
AU - Haber, Julia
AU - Katz, Gady
AU - Lindor, Keith
PY - 2002
Y1 - 2002
N2 - Background and Aims: The pathogenesis of primary biliary cirrhosis (PBC) is unknown. The role of cytokines such as tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), and the effect of ursodeoxycholic acid (UDCA) in modifying the cytokine environment in patients with PBC has remained largely unstudied. Our aims were to determine: (i) the relationship between serum levels of TNF-α and TGF-β and the severity of PBC; and (ii) the effects of UDCA therapy on TNF-α and TGF-β levels in patients with PBC. Methods: We studied 90 patients who had been treated with UDCA (53 patients) or placebo (37 patients) for 2 years as part of a randomized, double-blind, controlled trial. Patients were divided into histological stage I/II or stage III/IV disease. Serum TNF-α and TGF-β levels were quantified by enzyme-linked immunoabsorbent assay. Results: Baseline levels of TNF-α were significantly greater in patients with stage III/IV compared to stage I/II disease. After 2 years of treatment with UDCA, patients showed a significantly greater decrease in TNF-α levels and progression risk score compared to placebo-treated patients. TNF-α and TGF-β levels were significantly reduced compared to baseline levels in the UDCA-treated group after 2 years, while there was no significant change in the levels of placebo-treated patients. Conclusions: Serum TNF-α and TGF-β levels may reflect severity of disease in patients with PBC. The beneficial effects of UDCA therapy may be explained by lowering serum levels of these two cytokines.
AB - Background and Aims: The pathogenesis of primary biliary cirrhosis (PBC) is unknown. The role of cytokines such as tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β), and the effect of ursodeoxycholic acid (UDCA) in modifying the cytokine environment in patients with PBC has remained largely unstudied. Our aims were to determine: (i) the relationship between serum levels of TNF-α and TGF-β and the severity of PBC; and (ii) the effects of UDCA therapy on TNF-α and TGF-β levels in patients with PBC. Methods: We studied 90 patients who had been treated with UDCA (53 patients) or placebo (37 patients) for 2 years as part of a randomized, double-blind, controlled trial. Patients were divided into histological stage I/II or stage III/IV disease. Serum TNF-α and TGF-β levels were quantified by enzyme-linked immunoabsorbent assay. Results: Baseline levels of TNF-α were significantly greater in patients with stage III/IV compared to stage I/II disease. After 2 years of treatment with UDCA, patients showed a significantly greater decrease in TNF-α levels and progression risk score compared to placebo-treated patients. TNF-α and TGF-β levels were significantly reduced compared to baseline levels in the UDCA-treated group after 2 years, while there was no significant change in the levels of placebo-treated patients. Conclusions: Serum TNF-α and TGF-β levels may reflect severity of disease in patients with PBC. The beneficial effects of UDCA therapy may be explained by lowering serum levels of these two cytokines.
KW - Bile acids
KW - Cytokines
KW - Fibrosis
KW - Hepatocytotoxicity
KW - Immunomodulation
KW - Primary biliary cirrhosis
KW - Transforming growth factor-β
KW - Tumor necrosis factor-α
KW - Ursodeoxycholic acid
UR - http://www.scopus.com/inward/record.url?scp=0036226760&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0036226760&partnerID=8YFLogxK
U2 - 10.1046/j.1440-1746.2002.02672.x
DO - 10.1046/j.1440-1746.2002.02672.x
M3 - Article
C2 - 11966951
AN - SCOPUS:0036226760
SN - 0815-9319
VL - 17
SP - 196
EP - 202
JO - Journal of Gastroenterology and Hepatology (Australia)
JF - Journal of Gastroenterology and Hepatology (Australia)
IS - 2
ER -