Tumor necrosis factor-α and transforming growth factor-β reflect severity of liver damage in primary biliary cirrhosis
2002
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 (ΤGF-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.
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