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)

To determine whether release of tumor necrosis factor-alpha (TNF-alpha), a cytokine that affects iron homeostasis, may be selectively altered in hereditary hemochromatosis, we measured concentrations of TNF-alpha and interleukin-1 beta (IL-1 beta) in supernatants of cultured peripheral blood monocytes from 11 homozygotes for hereditary hemochromatosis, 11 healthy individuals, and five patients with iron-loading anemia. The gene for hereditary hemochromatosis is tightly linked to the HLA locus on chromosome 6, but its exact site and product are not known. The gene for TNF-alpha also is located within the HLA region. Monocytes were incubated from 4 to 36 hours in medium alone or with added lipopolysaccharide. Mean concentrations of immunoreactive TNF-alpha in supernatants were significantly lower for subjects with hereditary hemochromatosis as compared to healthy controls (P less than .037) and patients with iron-loading anemia (P less than .005); differences between homozygotes for hemochromatosis and healthy controls were up to 4.5-fold at 4 hours (P = .008), 1.9-fold at 12 hours (P = .036), and 7.0-fold at 36 hours (P = .001). Importantly, concentrations of IL-1 beta in supernatants were not significantly different among the three groups. We conclude that release of TNF-alpha by monocytes may be selectively impaired in hereditary hemochromatosis. Deficient activity of TNF-alpha may contribute to the disordered iron metabolism of this disease.
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PMID:Decreased concentrations of tumor necrosis factor-alpha in supernatants of monocytes from homozygotes for hereditary hemochromatosis. 155 77

Highly purified and cloned preparations of interleukin-1 (IL-1) were found to antagonize the capacity of erythropoietin (Epo) to stimulate the proliferation of mouse spleen and bone marrow erythroid precursor cells (EPC) in culture. Cloned murine IL-1 and purified and cloned human IL-1 alpha and IL-1 beta were approximately equipotent in this assay. IL-1 inhibited the proliferation response of EPC even when added as long as 17 h after Epo, suggesting that IL-1 does not affect binding of Epo to receptors or biochemical events following shortly thereafter. Indomethacin did not influence the inhibitory effect of IL-1 on Epo-induced proliferation, and PGE2 had no demonstrable effect on the process. Tumor-necrosis factor-alpha and interferons beta 1, and gamma did not affect Epo-induced proliferation. It is suggested that IL-1 mediated antagonism of the effects of Epo on erythroid precursors is a factor in the pathogenesis of many types of hypoplastic anaemia, including those associated with infections, rheumatoid arthritis and systemic lupus erythematosus, giant-cell arteritis, graft-versus-host disease and disorders associated with lymphocyte-mediated suppression of erythropoiesis.
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PMID:Inhibition by interleukin-1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias. 349 70

In vitro monocyte-derived tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) production was assessed in iron deficient with anemia (IDA), iron deficient without anemia (ID) and control infants. The concentrations of released and cell-associated cytokines were measured before and after 3 months of iron supplementation in all groups (ferrous sulphate drops: 3 mg/Kg/day). No difference in released and cell-associated IL-1 beta was observed between either groups of infants. Lipopolysaccharide-stimulated blood mononuclear cells from IDA (n = 9) infants produced a significantly higher immunoreactive TNF-alpha concentration as compared to ID (n = 9) and normal subjects (n = 18) on admission (F = 6.72; p < 0.004). After iron therapy, the LPS stimulated TNF-alpha secretion by cells of IDA infants returned to the levels observed in the other groups. Since TNF-alpha plays a key role in iron metabolism, we speculate that increased TNF production in IDA infants could exacerbate the inhibition of erythroid proliferation present in these conditions. Further studies are needed to evaluate the effect of more severe anemia as well as to clarify the biological effect of increased TNF-alpha production in iron deficiency anemia and its consequences.
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PMID:Increased in vitro tumour necrosis factor-alpha production in iron deficiency anemia. 784 56

Decreased production of erythropoietin (Epo) as a result of reduced renal mass is considered the main factor underlying the anaemia that is invariably associated with chronic renal failure (CRF). Other mechanisms such as accumulation of inhibitors of Epo also contribute. In this study we show that supernatant from peripheral blood mononuclear cells (PBMC) cultured from patients with CRF inhibits Epo release by Hep G2 cells in vitro. Ten patients (5 male) with CRF (mean age 42 years, range 25-60) were studied. Five were approaching end-stage renal failure and five were maintained on haemodialysis (HD). Ten apparently healthy volunteers were used as controls. Full blood counts and serum Epo (RIA) levels were determined and adherent PBMC were cultured for 48 h with and without LPS. There was a significant rise in TNF-alpha and IL1-beta levels measured in monocyte supernatant (MS) from patients and controls after LPS stimulation (P < 0.05) and in IL-1 alpha levels in patients (P < 0.05). IL-1 beta levels were higher in patients compared to controls both before and after stimulation with LPS (P < 0.05). Hep G2 cells were cultured in 5% CO2 and 20% O2 and incubated with MS from patients and controls for 24 h. Hep G2 harvest fluids were then analysed for Epo levels, which were expressed as a function of total cell protein (mU/mg). Epo production was inhibited by MS from patients compared to controls both before and after stimulation with LPS (P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peripheral blood mononuclear cells from patients with chronic renal failure release factors which suppress erythropoietin secretion in vitro. 797 Jan 19

Study was inspired by the suggestion that interleukin 1-beta (IL-1 beta), one of the major inflammatory mediators, is directly responsible for anaemia of chronic inflammatory conditions. Effect of IL-beta was studied in vitro on methyl cellulose cultures of normal human bone marrow cells, the inoculate having been previously highly enriched in progenitor and stem cells. Our data did not support results reported by others that IL-1 beta is a strong inhibitor of early stages of erythropoiesis in vitro measured by early and late BFU-E formation. About 30% statistically not significant CFU-E inhibition was observed. Above studies show that IL-1 beta role in the development of anaemia associated with chronic inflammatory diseases requires further studies.
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PMID:[In-vitro study of anemia in chronic inflammatory conditions. Effect of recombined interleukin-1 beta on human erythropoiesis]. 800 22

To define the toxicity profile of recombinant human interleukin-6 (rhIL-6) and to study its effect on hematopoiesis, biochemical parameters and other cytokines, rhIL-6 was administered in a phase I-II study to 20 patients with breast carcinoma or nonsmall cell lung cancer. RhIL-6 doses were 0.5, 1.0, 2.5, 5.0, 10, and 20 micrograms/kg/d, with at least three patients per dose level. RhIL-6 was administered 24 hours by continuous intravenous infusion followed by subcutaneous (SC) administration for 6 days, partly on an outpatient basis. RhIL-6-related side effects were fever, headache, myalgia, and local erythema. Starting at 2.5 micrograms/kg/d, these side effects were compounded by nausea, reversible increase in liver enzymes, and anemia. Flu-like symptoms were controllable up to and including 10 micrograms rhIL-6/kg/d with acetaminophen. RhIL-6 increased platelet counts with a decrease in mean platelet volume and increased leukocytes caused by neutrophil, monocyte, and lymphocyte increase, with an increase in T cells and natural killer cells at 1.0 and 2.5 micrograms rhIL-6/kg/d. The reversible anemia was characterized by a decrease in serum iron, and an increase in ferritin and erythropoietin without reticulocytosis. RhIL-6 reduced total cholesterol levels and a dose-related increase of C-reactive protein and serum amyloid A plasma levels was observed. Serum IL-6 levels were increased, especially at 10 and 20 micrograms/kg/d, whereas no change in IL-1 beta and tumor necrosis factor alpha levels was observed. RhIL-6 can be administered with controllable side effects in this setting, up to and including a SC dose of 10 micrograms/kg/d on an outpatient basis, and has a promising stimulating effect on leukopoiesis and thrombopoiesis.
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PMID:Effects of recombinant human interleukin-6 in cancer patients: a phase I-II study. 806 39

The enzyme immunoassay determined serum levels of interleukin-1 beta (IL-1 beta) in 35 patients with systemic lupus erythematosus (SLE) and 18 rheumatoid arthritis (RA) patients. In high activity of both SLE and RA as well as in the presence of fever, anemia, marked skin vasculitis IL-1 beta rose high, still higher levels being reported in patients with erosive joints compared to those in RA patients with initial stage of RA. Lower IL-1 beta content often marked nephropathy in both the diseases. Corticosteroids and cytostatics resulted in IL-1 beta fall which was also established in 9 SLE and 3 RA patients in parallel with inhibition of the process activity.
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PMID:[The content of interleukin-1 beta in the blood serum of patients with systemic lupus erythematosus and rheumatoid arthritis]. 814 72

Although PDGF is not a primary hematopoietic cytokine, effects in hematopoietic cell cultures have been reported. We recently described responses of multilineage hematopoietic precursors to PDGF. The effects were shown to be neutralized by antibody to IL-1 beta and mediated by marrow macrophages that expressed PDGF receptor RNA and responded to PDGF by upregulation of IL-1 RNA. The present study was performed to determine whether constitutive expression of PDGF by hematopoietic cells would have hematopoietic consequences in vivo. Retroviral vectors containing a PDGF-B gene were constructed and infected into normal marrow cells. Irradiated mice reconstituted with infected cells consistently developed a lethal myeloproliferative syndrome with anemia, neutrophilia and monocytosis, declining hematopoiesis in marrow with shift to the spleen, and extensive infiltration of immature hematopoietic cells into the parenchymal organs and connective tissues. In addition to PDGF, the retroviral constructs expressed a neo resistance marker. Phenotypic expression patterns in fibroblasts and in hematopoietic colony-forming cells in vitro were consistent with a significant degree of interaction between the two expressed inserts. Moreover, selection of infected cells for G418 resistance significantly reduced not only the number of infected reconstituting cells but also the intensity of the evoked syndrome in vivo. The observations have important implications for projected gene therapy protocols, and identify a novel potential pathway to myeloproliferative disease.
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PMID:Overexpression of PDGF-B in murine hematopoietic cells induces a lethal myeloproliferative syndrome in vivo. 830 75

Serum levels of monokines, including macrophage colony-stimulating factor (M-CSF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha) and IL-1 beta (IL-1 beta), were measured in patients with chronic renal failure in an attempt to clarify the kinetics of these cytokines in the course of renal anemia. M-CSF was the only monokine detectable in the serum from all patients as well as healthy donors, making this cytokine feasible and reliable for serial evaluations. On all occasions, the level of M-CSF in uremic patients was significantly higher than that in healthy donors (29.4 +/- 12.3 vs. 5.5 +/- 1.1 ng/mL). In patients undergoing hemodialysis, the serum level of M-CSF was greater than that in patients undergoing continuous ambulatory peritoneal dialysis or in uremic patients without dialysis therapy. No difference was observed, however, in the levels of IL-1 alpha, IL-1 beta and TNF-alpha levels in these groups. Patients with severe anemia were subsequently treated with 60 to 80 U/kg per week of human recombinant erythropoietin (rhEpo) for 3 months. After this replacement therapy, hemoglobin levels increased with a variable change ranging from 0 to 3.5 g/dL. The pretherapy M-CSF level, however, was found to predict statistically the response to the therapy (p < 0.05). Patients with a lower pretherapy value responded better to rhEpo therapy; those with a higher level showed a minor degree of response. From these results, we postulate that the elevated M-CSF serum level in uremic patients is in part a consequence of the dialysis procedure and that rhEpo therapy is more effective in patients who are under sophisticated dialysis protocol and have a lower M-CSF level.
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PMID:Measurement of serum levels of macrophage colony-stimulating factor (M-CSF) in patients with uremia. 842 60

During the last decade, the availability of large numbers of cytokines and growth factors has greatly favoured the use of biotherapies in several haematological disease. For MM, the majority of clinical studies have dealt with the use of IFN-alpha. From these studies it appears that IFN-alpha has a definite role in the treatment of MM especially in the setting of minimal residual disease, as maintenance therapy after response to conventional therapies or HDC followed by BMT procedures or PBSCI. Data on the use of EPO have consistently demonstrated the role of this growth factor in ameliorating the grade of anaemia as well as the quality of life of those MM patients whose disease is complicated by the presence of a severe or moderate anemia. Despite the large amount of experimental data indicating a role for IL-2 and IL-6 in controlling tumour growth, there are only a few clinical studies dealing with their use in MM. From these, it appears that IL-2 and anti-IL-6 antibodies should be further investigated as therapeutic tools useful in maintaining responses, because results show that they arrest tumour progression rather than aid, tumour regression. Finally, in the next years, there will be a wider diffusion of biotherapies in MM that should take into account the roles that IL-1 beta and TNF alpha play in myeloma cell proliferation and bone destruction and the finding that retinoic acid is capable of inhibiting the growth of human myeloma cells in vitro through modulation of IL-6 and its receptor.
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PMID:The role of biotherapies (interleukins, interferons and erythropoietin) in multiple myeloma. 884 74


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