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)

Interferon treatment is known to cause hematologic changes such as thrombocytopenia, anemia and granulocytopenia or combinations thereof. Patients previously treated with chemotherapeutic drugs followed by alpha interferon treatment developed even more severe pancytopenia and aplasia. Case reports of two patients who received treatment with alpha interferon 2a are reported here. Both patients were previously treated with chemotherapy, but with a long interval before starting IFN administration. Patient one developed life-threatening bone marrow hypoplasia and aplasia after interferon treatment and died. Patient two showed similar but less severe changes in bone marrow, i.e. thrombocytopenia, mild leukopenia and anemia. The clinical course of both patients was followed by routine peripheral blood tests and bone marrow biopsies and permit some reflection on the pathogenesis of marrow hypoplasia. Myelosuppressive effects of interferon treatment are discussed in the context of chemotherapy effects, cytokine actions and potential additional influences of herpesvirus infections.
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PMID:Bone marrow hypoplasia and fibrosis following interferon treatment. 789 89

Interferon-alpha (IFN-alpha) can inhibit human immunodeficiency virus (HIV-1) replication and is effective in treating Kaposi's sarcoma; interleukin-2 (IL-2) can increase circulating lymphocytes in HIV-1-infected patients. The safety of combination treatment with recombinant (r)IFN-alpha 2b and IL-2 was evaluated in HIV-1-infected patients with > 200 CD4+ T cells/mm3. A maximal tolerated dose of rIFN-alpha 2b was determined for 17 patients; then they received in combination 3, 6, or 12 x 10(6) IU/day rIL-2, given intravenously over 21 days. Twelve patients ultimately received the combination, 9 for the full 21 days. Significant toxicities included flu-like symptoms, anemia, transaminemia, and depression. Transient increases in CD4+ T cell percentages and spontaneous lymphocyte blast transformation were observed. Quantitative microcultures demonstrate a decline in HIV titers in patients receiving rIFN-alpha 2b (5/9) with a further decline on addition of rIL-2 (7/9). In summary, continuous rIL-2 at 6 x 10(6) IU/day in combination with rIFN-alpha 2b was reasonably tolerated and provided preliminary evidence of immunomodulatory and antiviral activity.
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PMID:A phase I study of interferon-alpha 2b in combination with interleukin-2 in patients with human immunodeficiency virus infection. 790 50

Following a three-week administration of alpha-interferon (IFN-alpha), a 62-year-old woman with chronic hepatitis C manifested fever and dyspnea and showed diffuse infiltrative opacities on chest roentgenograms. Her laboratory data included results of anemia with reticulocytosis, a decreased complement level and hepatitis with elevated ALP, LDH and gamma-GTP. Because laboratory data also revealed a positive lymphocyte stimulation test for IFN-alpha, this cytokine was considered to be responsible for the development of interstitial pneumonia, hemolytic anemia and cholestatic liver dysfunction due to its immunomodulatory effects. Although these three disorders have been reported to develop singly after IFN-alpha therapy, this is the first report of a patient in whom these disorders occurred simultaneously.
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PMID:A patient with chronic hepatitis C who simultaneously developed interstitial pneumonia, hemolytic anemia and cholestatic liver dysfunction after alpha-interferon administration. 791 19

Growth and differentiation of hematopoietic progenitor cells is regulated by a complex network of stimulatory and inhibitory cytokines. Bone marrow failures can be due to a decrease of stimulators or an increase of inhibitors. T cells produce both, hematopoiesis stimulating and inhibiting cytokines. Therefore, a role of T cells in regulating hematopoiesis can only be assumed if the gene expression of these antagonistic acting cytokines can be differentially induced in T cells. To establish a model of selective cytokine induction, we investigated the induction of IFN gamma as inhibitor and GM-CSF as stimulator of hematopoiesis in T cells. Our results showed that IFN gamma mRNA accumulates in T cells which have been pre-activated via the signal transduction unit CD3, but not in unstimulated T cells. This accumulation depends on the expression of the high affinity IL2 receptor which is including the IL2 receptor alpha-chain (IL2R alpha, CD25). In a study on children with constitutional (CAA) versus acquired aplastic (EAA) anemia, we investigated the relevance of this model for the pathogenesis of aplastic anemia in childhood. We compared the following parameters: 1. Incidence of hematopoietic progenitor cells and cloning efficiency, 2. activation status and IL2R alpha expression of bone marrow T cells, 3. T cell cytokine expression profile. Our results show: 1. The relative incidence of bone marrow progenitor cells is decreased in children with CAA and normal in children with EAA. 2. Clonogenic growth of hematopoietic progenitor cells is suppressed in children with EAA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Experimental principles of therapy-oriented pathogenetic classification of aplastic anemia in childhood]. 796 17

Anemia is a frequent manifestation of rheumatoid arthritis, with a probably multifactorial etiology. We investigated the effect of peripheral blood mononuclear cell supernatants (PBMCS) from rheumatoid arthritis (RA) patients on hematopoietic colony formation in vitro, by using a methylcellulose assay. PBMCS from patients suppress in vitro erythroid (BFU-E), mixed-lineage (CFU-GEMM) and to a lesser degree granulocyte-macrophage (CFU-GM) progenitors. PBMCS from anemic RA patients were more suppressive for BFU-E than those from non-anemic patients. Addition of antibodies to tumor-necrosis factor alpha (TNF alpha) almost completely reversed the inhibition of BFU-E and CFU-GEMM, but had little effect on the CFU-GM colony formation. Antibodies to interferon-gamma (IFN gamma) and interleukin-1 (IL-1) were not effective. The above data suggest that PBMCS from RA patients suppress in vitro erythropoiesis via the production of TNF alpha; a pathogenetic role for TNF alpha in the anemia of RA can be implied.
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PMID:Peripheral blood mononuclear cells from patients with rheumatoid arthritis suppress erythropoiesis in vitro via the production of tumor necrosis factor alpha. 806 94

Forty patients with AIDS-associated Kaposi's sarcoma (KS) treated with the combination of interferon alpha-2b (IFN-alpha) 10-20 MU day-1 and zidovudine (ZDV), 500-800 mg day-1, were evaluated for safety and efficacy. Eighteen patients (45%) had an overall response (CR+PR) at 3 months and a response persisting for a median of 14 (3-27) months. Patients with a CD4 count of less than 300 mm-3, prior to opportunistic infections or constitutional symptoms, were less likely to respond. However, between 28.5% and 36% of patients with a low CD4 count did respond to combined therapy. This is higher than would be predicted from single agent IFN-alpha therapy. Twelve of 28 patients (42.8%) receiving 10 MU day-1 of IFN-alpha (low dose) had an overall response. In addition, patients tolerated this dose of IFN-alpha better, presenting fewer flu-like symptoms and displayed a trend toward less anaemia. p24 antigen decreased in six out of nine evaluable cases, four of whom were treated with low-dose IFN-alpha. Low-dose IFN-alpha plus ZDV seems to be a useful and well-tolerated therapy for KS with antitumoral and antiviral activity. Patients without 'bad prognostic markers' are most likely to show improvement.
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PMID:Low-dose interferon alpha combined with zidovudine in patients with AIDS-associated Kaposi's sarcoma. 809 16

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

A 67-year-old male was admitted to our hospital because of anemia, thrombocytopenia, and renal failure. On admission he showed splenomegaly and elevated serum LDH level. Bone marrow showed hypercellularity with massive infiltration of lymphoblastoid cells. He was diagnosed as having multiple myeloma (BJ-kappa, stage IIIB). He transiently responded to intensive chemotherapy (VAD, MP, IFN alpha) but relapsed with multiple subcutaneous tumors and pericardial effusion. This is a rare case that the myeloma cell invasion to pericardial space was diagnosed before his death. The level of interleukin 6 (IL-6) in pericardial effusion was 16382 pg/ml, and the myeloma cells obtained from the pericardial effusion responded to IL-6, which suggested that high level of IL-6 closely related to the proliferation of myeloma cells in this case.
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PMID:[Aggressive myeloma with subcutaneous tumor and pericardial involvement]. 815 51

In patients with the anemia of chronic diseases, the plasma level of EPO is often low in relation to the blood hemoglobin concentration. Because infectious and inflammatory processes cause activation of cytokine-producing macrophages and lymphocytes, we investigated whether isolated inflammatory cytokines influence the synthesis of EPO in vitro. IL-1 and TNF-alpha were shown to inhibit EPO mRNA levels and EPO formation in the human hepatoma cell cultures HepG2 and Hep3B, and to lower EPO formation in isolated perfused rat kidneys. IFN-alpha and IFN-beta also induced some inhibition of EPO production in HepG2 cultures. IL-3, TGF-beta 2, and IFN-gamma did not inhibit. IL-6 stimulated the production of EPO in Hep3B cells but was ineffective in HepG2 cells and lowered EPO production in isolated perfused rat kidneys. IL-1, TNF-alpha, and possibly other cytokines could contribute to defective EPO production in renal and nonrenal immune responses.
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PMID:Inhibition of erythropoietin production by cytokines. Implications for the anemia involved in inflammatory states. 818 37

Interferons have been shown to increase in vitro cytotoxicity of platinum compounds. The Hoosier Oncology Group has conducted a Phase II clinical trial to determine if interferon alpha-2a (IFN-alpha-2a) given in combination with carboplatin (CBDCA) can increase response rates or survival in patients with metastatic or recurrent inoperable non-small-cell lung cancer. Forty-four patients with no prior chemotherapy and high KPS (80-100) were enrolled. CBDCA 400 mg/m2 was given intravenously on day 1 and IFN-alpha-2a 9 million units was given subcutaneously on days 1, 3, and 5. Treatment was administered every 4 weeks until onset of progressive disease or to a maximum of 4 courses: 37 patients (84%) received at least 2 courses, whereas only 16 (36%) received the full 4 courses. Dose-limiting toxicities were leukopenia (27%) and thrombocytopenia (20%) attributable to CBDCA. Grade 2-3 anemia occurred in 32%. Only 4-7% of patients experienced severe fever, fatigue, or flu-like symptoms attributable to interferon administration. Of 41 patients evaluable for response, there were no complete responses and only 3 (7.3%) partial remissions. The overall median survival was 6 months. The combination of CBDCA and IFN-alpha-2a given in this dose and schedule does not appear to have superior activity compared to CBDCA alone in patients with non-small-cell lung cancer.
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PMID:Carboplatin (CBDCA) plus alpha interferon in metastatic non-small cell lung cancer. A Hoosier Oncology Group phase II trial. 825 69


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