| Anaemia of chronic disease in AA amyloidosis is associated with allele 2 of the interleukin-1beta-511 promoter gene and raised levels of interleukin-1beta and interleukin-18. | |
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MedLine Citation:
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PMID: 15257727 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: In amyloid A (AA) amyloidosis the receptor for advanced glycation end products is a target for the circulating amyloid precursor protein (SAA) resulting in upregulation of the proinflammatory cytokine pathway. Besides inducing hepatic SAA synthesis the interleukin-1 cytokine family is involved in the regulation of haematopoiesis. We therefore studied the relationship between the circulating levels of interleukin-1beta (IL-1beta) and interleukin-18 (IL-18), a new member of the IL-1 complex, as well as polymorphisms within the IL-1 cluster with the occurrence of anaemia in patients with AA amyloidosis. DESIGN, SETTING AND SUBJECTS: The study included 54 adult patients with biopsy-proven reactive amyloidosis allocated into three groups on the basis of haemoglobin (Hb) level: group I included all patients with Hb < 110 g L(-1) (n = 16); group II patients (Hb > 110 g L(-1), n = 16) were selected to match group I patients with respect to sex, age, underlying disease (seropositive, erosive rheumatoid arthritis) and renal function; and group III patients (n = 38) represented all patients (unselected) with Hb > or = 110 g L(-1). Gene polymorphisms were studied by polymerase chain reaction restriction length assay and included the base exchange at position-889 of the IL-1alpha gene, the polymorphic region at position-511 and the polymorphic locus at exon 5, position +3954 of the IL-1beta gene, as well as the IL-1 receptor antagonist (IL-1Ra) exon 2 polymorphism caused by the 86-bp tandem repeats. Plasma IL-1beta, IL-1alpha, IL-18, IL-1 Ra, SAA, ferritin, soluble transferrin receptor and erythropoietin levels were studied by enzyme immunoassays. RESULTS: Circulating IL-beta and IL-18 were significantly raised in the anaemic patients with AA amyloidosis when compared with group II patients (matched, Hb > 110 g L(-1)) as well as group III patients (nonmatched, Hb > or = 110 g L(-1)). A significant inverse relationship was found between IL-1beta and haemoglobin levels, as well as between IL-18 and haemoglobin levels. The frequency of allele 2 (T) of the IL-1beta-511 promoter gene was significantly increased and that of allele 1 (C) decreased in anaemic amyloid patients (group I) when compared with group II and III patients. Circulating IL-1beta levels tended to be higher amongst the IL-1beta-511 allele 2 carriers than amongst the noncarriers, as well as amongst the anaemic amyloid patients filling all criteria of anaemia of chronic disease. CONCLUSION: The occurrence of anaemia in patients with AA amyloidosis is associated with allele 2 (T) of the IL-1beta-511 promoter gene and elevated levels of circulating IL-1beta and IL-18. In AA amyloidosis the raised cytokine levels may generate a vicious cycle leading to accelerated amyloidogenesis, suppression of erythropoiesis and aggravation of the underlying inflammatory disorder. |
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Authors:
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C P J Maury; M Liljeström; K Laiho; S Tiitinen; K Kaarela; M Hurme |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of internal medicine Volume: 256 ISSN: 0954-6820 ISO Abbreviation: J. Intern. Med. Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-07-19 Completed Date: 2004-09-16 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 8904841 Medline TA: J Intern Med Country: England |
Other Details:
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Languages: eng Pagination: 145-52 Citation Subset: IM |
Affiliation:
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Department of Medicine, University of Helsinki and University Central Hospital, Helsinki, Finland. peter.maury@hus.fi |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Amyloidosis / genetics*, immunology Anemia / genetics*, immunology Chronic Disease Female Humans Interleukin-1 / blood*, genetics* Interleukin-18 / blood* Male Middle Aged Polymorphism, Genetic Promoter Regions, Genetic Serum Amyloid A Protein / metabolism* Statistics, Nonparametric |
| Chemical | |
Reg. No./Substance:
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0/Interleukin-1; 0/Interleukin-18; 0/Serum Amyloid A Protein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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