| Abstrakt: |
Removal of iron by means of phlebotomy has been shown to reduce serum transaminase levels in chronic hepatitis C. If initial studies indicating no effect of phlebotomy therapy on serum viral RNA concentrations are proven to be correct, then other mechanisms such as cell membrane stabilization or alterations in immune response must be responsible for this salutory effect. The aim of this study was to determine the effect of iron reduction therapy by means of phlebotomy on serum Th1 and Th2 cytokines. In addition, serum TGF-β1 levels were determined as a marker of fibrogenesis. Twelve patients with interferon-resistant chronic hepatitis C were phlebotomized weekly until mild iron deficiency anemia was achieved. Serum ALT, HCV-RNA, and serum IL2, IL4, IL10, interferon γ, and TGF-β1 were measured. Phlebotomy achieved a significant reduction in serum transaminases without reducing the viral load. Serum IL4 was undetectable before and after phlebotomy. Serum IL10 levels increased modestly after iron reduction therapy, whereas both Th1 cytokines decreased with phlebotomy therapy. These changes in serum cytokines resulted in a significant reduction of the Th1/Th2 cytokine ratio (1.13 ± 0.33 before phlebotomy vs 0.45 ± 0.16 after phlebotomy, P = 0.03). TGF-β1 levels were lower in 9 of 12 patients after iron reduction therapy. The relative increase in Th2 over Th1 cytokines may explain, at least in part, the improvement in transaminases (without effects on viral replication) observed after iron reduction therapy. A Th2 predominance should predispose to immune tolerance with less cellular/cytokine-mediated cytotoxicity, thus contributing to attenuated hepatocellular injury without a change in viral load. Lesser inflammatory activity could, in turn, reduce fibrogenic stimuli and therefore increase the time required to develop cirrhosis. J. Trace Elem. Exp. Med. 13:327331, 2000. © 2000 Wiley-Liss, Inc. |
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