Regulation of ferritin: a specific role for interferon-alpha (IFN-α)? The acute phase response in patients treated with IFN-α-2b

Authors

  • T. C. Stam,

    1. Department of Surgical Oncology, University Hospital Rotterdam, Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands,
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  • A. J. G. Swaak,

    1. Department of Autoimmune Diseases, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Experimental and Clinical Immunology, Amsterdam, The Netherlands,
    2. Department of Rheumatology, Zuiderziekenhuis, Rotterdam, The Netherlands,
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  • W. H. J. Kruit,

    1. Department of Medical Oncology, University Hospital Rotterdam, Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands
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  • A. M. M. Eggermont

    Corresponding author
    1. Department of Surgical Oncology, University Hospital Rotterdam, Daniel den Hoed Cancer Centre, Rotterdam, The Netherlands,
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Professor A. M. M. Eggermont, MD, PhD, Department of Surgical Oncology, Daniel den Hoed Cancer Centre, PO Box 5201, 3008 AE Rotterdam, The Netherlands. Tel.: +31 10 4391911, fax: +31 10 4391011, e-mail: eggermont@chih.azr.nl.

Abstract

Background Adult onset of Still’s disease is characterized by very high serum ferritin levels, in disproportion with other acute phase proteins (APPs). Because interferon-alpha (IFN-α) was observed to cause hyperferritinaemia in three healthy people without increase of other APPs, we hypothesized that IFN-α stimulates specifically the synthesis of ferritin. To test this hypothesis, we studied ferritin and other APP levels in patients treated with IFN-α.

Patients and methods Fifteen patients treated with IFN-α-2b 3–5 times a week, as adjuvant treatment after excision of a high-risk melanoma, were compared with six patients without adjuvant treatment (controls). Serum levels of C-reactive protein (CRP) and secretory phospholipase A2 (sPLA2) were measured using ELISA. Levels of ferritin, alpha1-acid glycoprotein (AAG) and albumin were determined by nephelometry.

Results CRP was decreased significantly after 4 weeks (P < 0·01) in the patients treated with IFN-α compared with the nontreated patients, after 6 months of treatment it was still decreased although not significantly. Ferritin increased significantly in the IFN-α-treated patients: 187% of pretreatment value after 4 weeks and 217% after 6 months (P < 0·01), while ferritin levels decreased in the nontreated patients. AAG increased significantly in IFN-α-treated patients (107, 114%) compared with the control-patients (91, 76%) but differences were less compared with CRP and ferritin. sPLA2 had a variable course, while albumin remained constant within the normal range in both patient groups.

Conclusions IFN-α induced a significant increase in ferritin, with a significant decrease in CRP, little increase in AAG, varying response of sPLA2 and no change in albumin. This finding suggests a specific role for IFN-α in the synthesis or secretion of ferritin. This mechanism may also be involved in the marked hyperferritinaemia in adult onset of Still’s disease.

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