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

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 APPs₃ 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.