Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic inflammatory disorders are associated with an increased risk of patients developing anaemia. There is some evidence that cytokines released during cell-mediated immune responses are capable of inhibiting bone marrow haematopoiesis. In vitro, interferon gamma and tumour-necrosis factor alpha inhibit growth of erythroid precursor cells. The mode of action of these cytokines is probably associated with their antiproliferative capacity. Decrease of serum iron and increase of storage iron in patients appears to be a consequence of the defense strategy of macrophages during long-lasting inflammatory disorders. Decreased serum iron correlates to decreased haemoglobin concentrations. In view of this, the development of anaemia seems likely to result from the altered iron metabolism induced by stimulated macrophages. Low haemoglobin levels and associated hypoxia up-regulate the release of erythropoietin, which can explain why increased circulating erythropoietin is usually found in patients with anaemia.
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PMID:Immune activation and the anaemia associated with chronic inflammatory disorders. 189 33

Anaemia is a frequent complication in patients with human immunodeficiency virus type 1 (HIV-1) infection. We tested 14 children with severe haemophilia (9 HIV-1 antibody seropositive CDC stage IIA, 5 seronegative) for haemoglobin and urinary neopterin concentrations and found a negative correlation between neopterin and haemoglobin (rs = -0.745, p = 0.007; Spearman's rank correlation). This finding suggests that chronic immune activation, possibly along with the release of specific cytokines such as interferon gamma and tumor necrosis factor alpha may be involved in the pathogenesis of anaemia.
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PMID:Low haemoglobin in haemophilia children is associated with chronic immune activation. 202 56

Acute visceral leishmaniasis is associated with an antigen-specific immunosuppression of mononuclear cells as evidenced by defective in vitro production of interferon gamma. We evaluated treatment with recombinant human interferon gamma in combination with conventional pentavalent antimony therapy in patients with visceral leishmaniasis. Six of eight patients with visceral leishmaniasis (mean duration, 17 months) that had been unresponsive to multiple courses of pentavalent antimony responded to treatment with recombinant human interferon gamma (100 to 400 micrograms per square meter of body-surface area per day) in addition to pentavalent antimony (20 mg per kilogram of body weight per day) for 10 to 40 days. The other two patients improved initially but then relapsed and required treatment with amphotericin B. Eight of nine additional patients with previously untreated severe visceral leishmaniasis were also successfully treated with the combination of interferon gamma and pentavalent antimony. The 14 patients who responded to this regimen had marked improvement in symptoms and in measures of anemia and leukopenia, as well as weight gain, a decrease in spleen size, and an absence or reduction of leishmanias in splenic aspirates. These patients had no recurrence of illness after a mean (+/- SE) follow-up of 8 +/- 1 months. Fever was the only major side effect of interferon gamma. We conclude that the combination of interferon gamma and pentavalent antimony is effective in treating seriously ill patients with refractory or previously untreated visceral leishmaniasis.
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PMID:Treatment of visceral leishmaniasis with pentavalent antimony and interferon gamma. 210 67

Experimental cerebral malaria (ECM), a lethal hyperacute neurological syndrome associated with high blood levels of tumor necrosis factor, develops in genetically susceptible (CBA/Ca) mice 7 days after infection with Plasmodium berghei ANKA strain. Injections of neutralizing monoclonal antibody against recombinant murine interferon gamma, not later than 4 days after infection, markedly reduced the incidence of ECM and the elevation in serum levels of tumor necrosis factor. This treatment prevented the cerebral lesions (plugging of brain vessels by monocytes, lymphocytes, and parasitized erythrocytes). In contrast, the extent of macrophage infiltration in lymphoid organs (which is a characteristic feature of mice developing ECM), as well as the course of infection, remained unaffected by the antibody treatment. Protected mice died at a later time of severe anemia and overwhelming parasitemia, the usual outcome of P. berghei infection in mice that are not susceptible to ECM. The present data indicate that interferon gamma constitutes an important link in the cytokine network that leads to brain vessel inflammation in experimental malaria. It is proposed that interferon gamma released by activated CD4+ T cells acts by augmenting both production and action of tumor necrosis factor.
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PMID:Monoclonal antibody against interferon gamma can prevent experimental cerebral malaria and its associated overproduction of tumor necrosis factor. 250 93

Efficacy and practicability of a defined dosage scheme for interferon gamma was proved during one year's treatment in patients with rheumatoid arthritis. Interferon gamma was well tolerated. It was effective in improving blood sedimentation rate, anemia, leucocytosis and thrombocytosis as well as clinical parameters such as pain, mobility, swollen joints and morning stiffness. Concomitant medication with corticosteroids could be reduced.
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PMID:[Interferon gamma in the treatment of chronic polyarthritis. Long-term therapy in clinical practice]. 250 69

We treated 11 patients who had Philadelphia-chromosome-positive chronic myelogenous leukemia with natural interferon alpha (human lymphoblastoid interferon; HLBI). HLBI was given at 6-12 X 10(6) u/day i.m. or i.s.c. during induction therapy. Nine patients responded to the treatment, of whom 7 had hematologic remission and 2 had partial remission. Six patients with MDS or hypoplastic leukemia, and 3 patients with overt leukemia from MDS were treated with recombinant interferon gamma (GI-3). GI-3 was given at 0.4 X 10(6) u/m2 of body-surface area per day i.s.c. or i.v. for 4-6 weeks. In 2 patients with RAEB and hypoplastic leukemia, the blast cell count in bone marrow decreased from 8-16% to 2-3% after 4 weeks of administration. In another patient with hypoplastic leukemia, blast cells in the marrow did not decrease, but anemia was improved without transfusion, increasing the bone marrow NCC and erythroblast count. In patients with overt leukemia and CMML, no clinical effect was obtained. Interferons can therefore be offered to patients in a preleukemic state.
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PMID:[Clinical investigation of interferons in the preleukemic state (CML and MDS)]. 313 93

Highly purified human blood burst-forming units-erythroid (BFU-E) were used to study the effects of interferon gamma (IFN gamma). IFN gamma inhibited erythroid colony formation, cell proliferation, and differentiation of day 3 to day 6 mature BFU-E in a dose-dependent manner. The primitive BFU-E (day 1 and day 2 cells) and later day 7 cells were less affected. IFN gamma dose-response experiments demonstrated that the number and size of erythroid colonies were reduced at a concentration of 500 U/ml with more complete inhibition at 1,000 U/ml. Inhibition of day 4 to day 6 erythroid progenitors was first noted by 72 h of incubation with IFN gamma, and target cell growth and differentiation continued to decrease with further incubation. IFN gamma also induced erythroblast apoptosis which was demonstrated by both nuclear condensation and fragmentation plus flow cytometry with in situ end-labelling. Because day 3 to day 6 cells need stem cell factor (SCF) for development in serum-free culture, the relationship of IFN gamma inhibition to this growth factor was investigated. The reduction in the number of erythroid colonies by IFN gamma was reversed by SCF although the colony size was not completely re-established. In contrast, interleukin-3 did not have the capacity to overcome the inhibitory effects of IFN gamma. Since IFN gamma blood levels are elevated in some anemias of chronic disease, IFN gamma may have a role in promoting this anemia and its inhibitory effect might be better overcome by SCF plus EP. However, the mechanism by which these growth factors overcome the inhibition of IFN gamma, or vice versa, is unknown at the present time.
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PMID:Stem cell factor can overcome inhibition of highly purified human burst-forming units-erythroid by interferon gamma. 759 10

It has been previously reported that inhibition of human erythroid colony-forming units (CFU-E) in vitro by interleukin-1 (IL-1) is an indirect effect, occurring through the production of interferon gamma (IFN gamma). IFN gamma, in turn, inhibits CFU-E colony formation directly, and its inhibitory effect can be overcome by exposure to high concentrations of erythropoietin (EPO). To develop an in vitro animal model for investigating inhibition of erythropoiesis by IFN gamma, the effects of recombinant murine (rm) IFN gamma on highly purified CFU-E from the spleens of mice infected with the anemia strain of the Friend virus (FVA) were studied. rmIFN gamma inhibited CFU-E colony formation in a dose-dependent manner. This inhibition occurred with large (> or = 8 cell) colonies only; smaller colonies were not affected. The inhibitory effect was corrected to 72% of control by high EPO concentrations of 64 U/mL. Murine CFU-E were then cultured with rmIFN gamma in the presence of a soluble murine IFN gamma receptor fused to the hinge and Fc domains of the human IgG1 heavy chain (mIFN gamma R-IgG). Inhibition of CFU-E colony formation by rmIFN gamma (100 U/mL) was corrected by mIFN gamma R-IgG in a dose-dependent manner, with an approximate IC50 of 0.05 nmol/L, and complete or near complete correction at 0.5 nmol/L. Similarly, a human IFN gamma R-IgG greatly reduced the inhibitory effect of recombinant human IFN gamma on human CFU-E. These experiments provide an in vitro animal model for studying the inhibitory effects of IFN gamma on erythropoiesis and indicate that IFN gamma R-IgG may be a useful agent for reducing the toxicity of IFN gamma in vivo.
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PMID:Inhibition of murine erythroid colony formation in vitro by interferon gamma and correction by interferon receptor immunoadhesin. 811 Oct 63

Fanconi anemia (FA) is an autosomal recessive chromosome instability syndrome characterized by progressive bone marrow (BM) failure, skeletal defects, and increased susceptibility to malignancy. FA cells are hypersensitive to DNA cross-linking agents, oxygen and have cell cycle abnormalities. To develop an animal model of the disease we generated mice homozygous for a targeted deletion of exon 9 of the murine FA complementation group C gene (fac). Mutant mice had normal neonatal viability and gross morphology, but their cells had the expected chromosome breakage and DNA cross-linker sensitivity. Surprisingly, male and female mutant mice had reduced numbers of germ cells and females had markedly impaired fertility. No anemia was detectable in the peripheral blood during the first year of life, but the colony forming capacity of marrow progenitor cells was abnormal in vitro in mutant mice. Progenitor cells from fac knock-out mice were hypersensitive to interferon gamma. This previously unrecognized phenotype may form the basis for BM failure in human FA.
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PMID:Germ cell defects and hematopoietic hypersensitivity to gamma-interferon in mice with a targeted disruption of the Fanconi anemia C gene. 870 1

Cattle undergoing initial infection with the rickettsia Anaplasma marginale were treated with either a monoclonal antibody (MoAb) with neutralizing activity for bovine interferon gamma (IFN-gamma) or aminoguanidine (AG), a specific inhibitor of the inducible form of nitric oxide synthetase (iNOS). Plasma levels of MoAb and AG were measured over the time of administration. The course of A. marginale infection was not altered in the MoAb-treated cattle relative to untreated controls. In cattle treated with AG however, A. marginale infection was significantly ameliorated, as judged by lower parasite levels and decreased anaemia in these cattle relative to the controls. The implications of these findings in relation to the basis for immunity against this economically important haemoparasite are discussed.
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PMID:Anaplasma marginale: effect of the treatment of cattle with an interferon gamma-neutralizing monoclonal antibody or the nitric oxide synthetase inhibitor aminoguanidine on the course of infection. 934 17


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