Radioactive Iron Metabolism and Erythrocyte Survival Studies of the Mechanism of the Anemia Associated with Rheumatoid Arthritis1

Freireich, Emil J.; Ross, Joseph F.; Bayles, Theodore B.; Emerson, Charles P.; Finch, Stuart C.

doi:10.1172/jci103500

Cited by 82 publications

(30 citation statements)

References 25 publications

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“…Early work using the Ashby (differential agglutination) technique suggested that there was a modest decrease in red cell survival in patients with the anaemia of RA (Freireich et a., 1957a), but later studies using 5'Cr labelling failed to show any significant alteration in red cell survival (Lewis and Porter, 1960; Mongan and Jacox, 1964). More recently, calculations of mean cell life have been made from ferrokinetic data using a computer assisted technique (Ricketts, Jacobs and Cavill, 1975).…”

Section: Laboratory Features and Differential Diagnosismentioning

confidence: 99%

The anaemia of chronic disorders

Samson¹

1983

Postgraduate Medical Journal

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Chronic disease can cause anaemia in a number of ways, such as poor nutrition, chronic blood loss and as a result of drug therapy. Leaving aside these factors, however, there is a specific type of anaemia associated with chronic infection, chronic inflammatory diseases and malignancy. This anaemia is characterised by decreased plasma iron and iron-binding capacity in the presence of normal or increased reticulo-endothelial iron stores, and has been termed the anaemia of chronic disorders (Cartwright and Lee, 1971). Although the anaemia of chronic disorders is one of the most common anaemias encountered in medical practice, its aetiology remains unclear and treatment unsatisfactory.

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Section: Laboratory Features and Differential Diagnosismentioning

confidence: 99%

The anaemia of chronic disorders

Samson¹

1983

Postgraduate Medical Journal

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“…Anemia commonly occurs in chronic infection, inflammation, and malignancy (1)(2)(3)(4). This anemia is characReceived for publication 14 June 1973 and in revised form 10 December 1973. terized by: (a) decreased plasma iron and iron-binding capacity; (b) impaired release of reticuloendothelial iron into the plasma; (c) modest decrease of red cell survival; and (d) relative failure of bone marrow to increase red cell production (1)(2)(3)(4)(5)(6)(7).…”

Section: Introductionmentioning

confidence: 99%

“…This anemia is characReceived for publication 14 June 1973 and in revised form 10 December 1973. terized by: (a) decreased plasma iron and iron-binding capacity; (b) impaired release of reticuloendothelial iron into the plasma; (c) modest decrease of red cell survival; and (d) relative failure of bone marrow to increase red cell production (1)(2)(3)(4)(5)(6)(7). These clinical similarities have resulted in the classification of these anemias in a single category, the anemia of chronic disorders (ACD)1 (8).…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow Erythropoiesis in the Anemia of Infection, Inflammation, and Malignancy

Zucker¹,

Friedman²,

Lysik³

1974

J. Clin. Invest.

102

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A B S T R A C T A major factor in the anemia of infection, inflammation, and malignancy is a relative failure of the bone marrow to increase erythropoiesis in response to a shortened red cell survival. The possible causes for this diminished marrow response are: (a) a reduced production of erythropoietin, or, (b) impaired bone marrow response to erythropoietin. In this report studies were performed on 6 normals, 13 patients with anemia from infection or inflammation, and 18 patients with anemia caused by advanced malignancy. Serum erythropoietin activity was measured using the posthypoxic, polycythemic mouse assay. Assessment of bone marrow response to erythropoietin was made by measuring '9Fe-heme synthesis in bone marrow suspensions cultured for 3 days with and without the addition of erythropoietin. The results showed that marrow heme synthesis was increased in erythropoietin-treated cultures as compared with saline control cultures by 66± 8% (mean +SE) in normals, 101±10% in patients with infection or inflammation, and 31±5% in malignancy.Serum erythropoietin levels were consistently diminished relative to expected levels for the degree of anemia in the infection-inflammatory group, but not in malignancy.In these patients, plasma inhibitors to the biological activity of erythropoietin were not detected in vitro.These studies suggest that another factor to consider in the anemia of malignancy is a decreased bone marrow response to erythropoietin. In the anemia of infectioninflammation, marrow response to erythropoietin is normal, but serum levels of erythropoietin are decreased relative to the degree of anemia.

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“…Anemia commonly occurs in chronic infection, inflammation, and malignancy (17)(18)(19)(20). A major factor in the anemia of infection, inflammation, and malignancy is a relative failure of the bone marrow to increase erythropoiesis in response to shortened red cell survival.…”

mentioning

confidence: 99%

Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse

Cuzzocrea

Mazzon

Paola

et al. 2005

Arthritis & Rheumatism

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Objective. Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells, and its expression is enhanced by hypoxia. The aim of this study was to investigate the effect of EPO on collagen-induced arthritis (CIA) in the mouse.Methods. CIA was induced by intradermal injection of bovine type II collagen (CII) and Freund's complete adjuvant. Starting on day 25, some of the mice with CIA received daily subcutaneous injections of EPO (1,000 units/kg). Two other groups of mice received sham treatment alone or sham treatment followed by EPO treatment, respectively. Arthritis was assessed clinically, radiologically, and histologically. Cytokine and chemokine levels were measured, and neutrophil infiltration into inflamed joints was quantitated. Immunohistochemistry studies were performed to measure protein nitrosylation. Chondrocyte apoptosis was assessed by TUNEL assay.Results. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by day 27 in the CII-challenged mice, and the severity of CIA progressed over a 35-day period, with radiographic evaluation revealing focal resorption of bone. Histopathologic features of CIA included erosion of the cartilage at the joint margins. Treatment with EPO starting at the onset of arthritis (day 25) ameliorated the clinical signs on days 26-35 and improved histologic status in the joints and paws. The degree of oxidative and nitrosative damage was significantly reduced in EPO-treated mice as indicated by decreased nitrotyrosine formation and poly(ADP-ribose) polymerase activation. Plasma levels of the proinflammatory cytokine tumor necrosis factor ␣ were also significantly reduced by EPO treatment. In addition, EPO reduced the levels of apoptosis in chondrocytes in articular cartilage, as indicated by decreased TUNEL staining.Conclusion. These findings demonstrate that EPO exerts an antiinflammatory effect during chronic inflammation and is able to ameliorate the tissue damage associated with CIA.

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Radioactive Iron Metabolism and Erythrocyte Survival Studies of the Mechanism of the Anemia Associated with Rheumatoid Arthritis1

Cited by 82 publications

References 25 publications

The anaemia of chronic disorders

The anaemia of chronic disorders

Bone Marrow Erythropoiesis in the Anemia of Infection, Inflammation, and Malignancy

Erythropoietin reduces the degree of arthritis caused by type II collagen in the mouse

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