Regulation of ferritin: a specific role for interferon-alpha (IFN-alpha)? The acute phase response in patients treated with IFN-alpha-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-alpha) was observed to cause hyperferritinaemia in three healthy people without increase of other APPs, we hypothesized that IFN-alpha stimulates specifically the synthesis of ferritin. To test this hypothesis, we studied ferritin and other APP levels in patients treated with IFN-alpha.


METHODS
Fifteen patients treated with IFN-alpha-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-alpha compared with the nontreated patients, after 6 months of treatment it was still decreased although not significantly. Ferritin increased significantly in the IFN-alpha-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-alpha-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-alpha 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-alpha in the synthesis or secretion of ferritin. This mechanism may also be involved in the marked hyperferritinaemia in adult onset of Still's disease.
Stam
T C
TC
Department of Surgical Oncology, University Hospital Rotterdam, Daniel den Hoed Cancer Centre, 3008 AE Rotterdam, The Netherlands.
Swaak
A J G
AJ
Kruit
W H J
WH
Eggermont
A M M
AM
D000210:Acute-Phase Reaction / Q000276:immunology / Q000378:metabolism; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002097:C-Reactive Protein / Q000378:metabolism; D005260:Female; D005293:Ferritins / Q000097:blood / Q000276:immunology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008545:Melanoma / Q000188:drug therapy; D008875:Middle Aged; D010741:Phospholipases A / Q000097:blood; D054467:Phospholipases A2; D011994:Recombinant Proteins; D012878:Skin Neoplasms / Q000188:drug therapy; D016706:Still's Disease, Adult-Onset / Q000097:blood / Q000188:drug therapy* / Q000276:immunology*
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D002097:C-Reactive Protein; D005293:Ferritins; D010741:Phospholipases A; D054467:Phospholipases A2