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)

Although IL-12 has been reported to synergize with c-kit ligand (KL) in promoting hematopoietic stem cell proliferation in vitro, administration of recombinant mouse IL-12 (rIL-12) to normal mice caused a dose- and time-dependent anemia, leukopenia, and thrombocytopenia in vivo. Decreased numbers of bone marrow cells were recovered from the tibiae of IL-12-treated mice, and histologic examination of the marrow revealed a loss of mature neutrophils and red blood cell precursors. However, simultaneously with the suppression of hematopoiesis in the bone marrow, the IL-12-treated mice developed splenomegaly, which was largely caused by a marked enhancement of splenic extramedullary hematopoiesis of the erythroid, myeloid, and megakaryocytic lineages. These histologic observations were confirmed by colony-forming cell assays in which administration of IL-12 was shown to cause a time-dependent decrease in bone marrow CFU-GM, CFU-E, and BFU-E hematopoietic colony-forming cells while causing an increase in splenic CFU-GM and BFU-E colony-forming cells. All these effects were reversible upon cessation of IL-12 treatment. The observation that in IL-12-treated mice hematopoiesis was suppressed in the marrow but enhanced in the spleen suggests that myelosuppression was not caused by a direct effect of IL-12 on hematopoietic progenitors. It seems likely that myelosuppression was caused instead by an IL-12-induced alteration in the local environment of the marrow.
J Interferon Cytokine Res 1995 Apr
PMID:Administration of recombinant interleukin-12 to mice suppresses hematopoiesis in the bone marrow but enhances hematopoiesis in the spleen. 762 13

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.
Eur Cytokine Netw
PMID:Increased in vitro tumour necrosis factor-alpha production in iron deficiency anemia. 784 56

The therapeutic efficacy of recombinant human leukemia inhibitory factor (LIF) was examined in a nonhuman primate model of radiation-induced marrow aplasia. Rhesus monkeys received 450 cGy of total-body, 1:1 mixed neutron:gamma radiation. For 23 days thereafter, each monkey received a daily subcutaneous injection of LIF or human serum albumin (HSA) at a dose of 15 micrograms/kg body weight. Complete blood counts and white blood cell differentials were monitored for 60 days postirradiation. Administration of LIF significantly decreased (P < or = .05) the duration of thrombocytopenia (platelet count < 30,000 or 20,000/microL), ie, 9.3 days or 6.3 days, respectively, versus the HSA-treated control monkeys, 12.2 days or 10.2 days, respectively. Treatment with LIF did not alter the duration of neutropenia (absolute neutrophil count < 1,000/microL) as compared with the HSA-treated control monkeys. Cytokine administration did not exacerbate the radiation-induced anemia observed in the HSA-treated control monkeys.
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PMID:Therapeutic efficacy of recombinant human leukemia inhibitory factor in a primate model of radiation-induced marrow aplasia. 794 22

The immature erythroid cell line J2E responds to erythropoietin (Epo) by proliferating and terminally differentiating into hemoglobin-synthesizing red blood cells. These cells produce a rapid, fatal erythroleukemia in mice characterized by hepatosplenomegaly and severe anemia. The aim of this study was to investigate the effects of murine interferons-alpha (MuIFN-alpha) on J2E cells in vitro and in vivo. Here we show that in culture MuIFN-alpha inhibited the Epo-induced proliferation of J2E cells but did not interfere with differentiation. When mice with J2E erythroleukemias were treated with MuIFNs in vivo, an extension of their life span was observed. Moreover, numerous necrotic lesions of infiltrating leukemic cells were detected in the spleens of these mice. Finally, ex vivo treatment of leukemic bone marrow cells with Epo and MuIFNs delayed mortality even further. It was concluded that MuIFNs (1) suppressed the proliferation of J2E cells in vitro but did not affect Epo-induced differentiation, and (2) inhibited the progress of erythroleukemias, especially in combination with Epo.
J Interferon Cytokine Res 1995 Aug
PMID:Interferon-alpha inhibits erythropoietin-induced proliferation, but not differentiation, and restricts erythroleukemia development. 852 38

To examine a possible association between plasma viremia and interferon-alpha (IFN-alpha) in patients with the acquired immunodeficiency syndrome (AIDS), we performed IFN plasma immunoadsorption by apheresis (IFN-alpha apheresis) in four volunteers with AIDS who had sustained levels of endogenous plasma IFN-alpha. IFN-alpha apheresis with two plasma volume exchanges was performed daily for 5 days. Clinical signs and symptoms and hematologic, virologic, and immunologic parameters were monitored. Two subjects developed anemia from phlebotomy, and one had a catheter++-associated bacteremia. The IFN-alpha apheresis was effective only in transiently removing IFN-alpha: depletion of IFN-alpha led only to its rapid reconstitution. Cell-associated HIV-1 was unchanged, but three of four subjects had a modest decrease in culturable plasma virus burden following the procedures. The recovery of in vivo HIV-1-related IFN-alpha by apheresis allowed its biologic and biochemical characterization. The HIV-1 IFN-alpha showed characteristics on ELISA, western blot, and biologic assays similar to two subspecies of the natural protein. The natural, recombinant, and HIV-1-induced IFN-alpha s demonstrated nearly identical antiviral activities. The HIV-1 IFN-alpha eluted from the column was not acid labile. The inability of large amounts of plasma IFN-alpha found in some patients with AIDS to affect viral burden likely reflects properties of the virus or of host factors independent of IFN-alpha.
J Interferon Cytokine Res 1996 Feb
PMID:Regulation and characterization of the interferon-alpha present in patients with advanced human immunodeficiency virus type 1 disease. 874 65

The aim of this pilot study was to investigate if chemotherapy (CT) followed by the combination of interferon-beta (IFN-beta), retinoids, and tamoxifen could be effective in the treatment of metastatic breast cancer (MBC). Thirty-six patients with stage IV carcinoma of the breast were treated with six courses of cyclophosphamide, 5-fluorouracil, 4-epidoxorubicin, vincristine, and prednisone every 3 weeks (FECPV), followed by two courses of non-cross-resistant drugs, methotrexate, mitomycin C, and mitoxantrone (MMM). Treatment was continued, in responders, with low dose IFN-beta, retinyl palmitate, and tamoxifen until relapse of the disease occurred. Among 36 evaluable patients, 23 achieved a clinical response (64 %) (95 % confidence interval [c.i.] 46 %-79 %), 7 had stable disease (19%), and 6 (17%) progressed. Leukopenia occurred in 15 patients, thrombocytopenia in 6, and anemia in 11. Sixteen patients had nausea/vomiting, stomatitis was observed in 9, and diarrhea occurred in 3. Toxicity from maintenance therapy was mild and mainly hepatic. Median response duration was 31 months (range 5-107). Median overall survival was 32 months (9-108). Our study shows that this combined approach for the treatment of MBC is feasible, with an acceptable toxicity.
J Interferon Cytokine Res 1998 Jan
PMID:Minimal residual disease in metastatic breast cancer: treatment with IFN-beta, retinoids, and tamoxifen. 947 66

Previous data suggested interaction of cisplatin with interferon (IFN) in non-small cell lung cancer and a possible effect of IFN in maintaining remission in small cell lung cancer (SCLC). This study was designed to further examine the effect of IFN in the treatment of extensive disease (ED) SCLC. Forty previously untreated patients with performance status (PS) of 0-2 (Zubrod scale) were treated with etoposide (100 mg/m2 for 3 days), cisplatin (25 mg/m2 for 3 days) (EP), and recombinant IFN-alpha2a (rIFN-alpha2a) (5 x 10(6) U/m2 for 3 days) for six cycles (induction), followed by rIFN-alpha2a (5 x 10(6) U/m2) thrice weekly and megestrol acetate (40 mg q.i.d.) as maintenance therapy for 6 months or until progressive disease or intolerable toxicity was documented. Patients were 25 men (62%) and 15 women (38%), median age 58 (28-76), median Zubrod performance status 1 (0-2). Major sites of metastasis include liver (55%), bone (42%), bone marrow (25%), and adrenal gland (18%). Of 40 eligible patients accrued to this trial, 35 were evaluable for response, and 37 were evaluable for toxicity. There were 3 complete and 28 partial responses, for an overall response rate of 89%. With 39 of 40 patients followed until death, median survival (Kaplan-Meier) is estimated at 46 weeks (95% CI range 35-55). Twenty patients completed six cycles of induction, and 16 received maintenance therapy, median 2 cycles (range 1-3). Major toxicity during induction included grade 4 granulocytopenia in 24%, grade 2-3 nausea or vomiting or both in 41%, grade 2 fatigue in 24%, grade 2 anorexia in 22%, and grade 2-3 renal insufficiency in 9% of 175 total courses of chemotherapy administered. Toxicity during the maintenance phase was notable for grade 2-3 fatigue in 43%, grade 2-3 anorexia in 24%, grade 2-3 weight loss in 10%, and grade 3-4 anemia in 17% of 30 courses. There were no treatment-related deaths. The addition of rIFN-alpha2a to EP in induction chemotherapy of ED SCLC, followed by rIFN-alpha2a and megestrol acetate maintenance therapy, was reasonably well tolerated. The complete and overall response rates and duration of remission and survival appear to be similar to those generally obtained with EP alone in similar patients.
J Interferon Cytokine Res 1998 Apr
PMID:Phase II trial of recombinant IFN-alpha2a with etoposide/cisplatin induction and interferon/megestrol acetate maintenance in extensive small cell lung cancer. 956 26

Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-1alpha (IL-1alpha), and interferon-gamma (IFN-gamma) were estimated by conventional ELISA kits in 60, 42, and 58 Thai patients, respectively, with beta(o)-thalassemia HbE and found to be above the normal range in 13%, 21%, and 33% of the patients, respectively. Using high-sensitivity ELISA systems, an additional 10 beta(o)-thal/HbE patients were compared with 9 controls for concentrations of circulating TNF-alpha and IL-1beta, and 9 and 5 patients, respectively, but only 1 and none of the controls, respectively, showed values above the normal ranges. In patients with abnormally high IFN-gamma levels, basal hemoglobin values were significantly lower than in those with normal levels of the cytokine (mean +/- SEM: 6.03+/-0.24 vs. 7.08+/-0.18, p < 0.05), although circulating concentrations of soluble transferrin receptors (sTrF) and absolute reticulocyte counts were similar in the two groups. Patients with raised or normal levels of TNF-alpha, IL-1alpha, or IL-1beta had similar basal hemoglobin values. In a phagocytosis assay, monocytes of patients with raised serum levels of IFN-gamma showed significantly more attached or ingested IgG-coated red cells than those of patients with normal concentrations of the cytokine (mean +/- SEM: 192+/-22 vs. 140+/-14 per 100 monocytes, p < 0.05). Moreover, in 3 of 4 of the former patients, the number of attached or ingested IgG-coated red cells per 100 monocytes was above the 95% reference limit for the latter patients. The results suggest that IFN-gamma aggravates the anemia of beta(o)-thal/HbE by activating mononuclear phagocytes for destruction of red cells but not by inhibiting erythropoiesis. The elevated serum levels of TNF-alpha and IL-1 could contribute to complications of the disease, such as cachexia and thromboembolic phenomena.
J Interferon Cytokine Res 1999 Feb
PMID:Serum levels of tumor necrosis factor-alpha, interleukin-1, and interferon-gamma in beta(o)-thalassemia/HbE and their clinical significance. 1009 Mar 95

The influence of hepatitis B (HBV) and hepatitis C virus (HCV) infection on blood hemoglobin (Hb) and serum erythropoietin (Epo) and interleukin-6 (IL-6) concentrations was studied in 48 anemic patients on regular hemodialysis. They were grouped as follows: (I) 19 patients whose Hb values improved after infection (Hb > 85 g/L), (II) 10 patients with persisting anemia after infection (Hb < 75 g/L), and, without hepatitis virus markers (III) 8 patients with Hb > 85 g/L and (IV) 11 patients with Hb < 75 g/L. Serum immunoreactive Epo levels were significantly higher in group I (34.4+/-47.1 U/L) than in the other groups (II, 10.8+/-6.0; III, 7.9+/-3.2; IV, 8.4+/-4.3). Serum IL-6 was higher in group I than group III (7.7+/-7.8 pg/ml vs. 3.6+/-2.4; p = 0.05) but similar to the other groups. Hb levels in group I were maximal at the time of serum alanine aminotransferase normalization. Red cell production increases as a result of elevated circulating Epo during hepatic regeneration after HBV or HCV infection.
J Interferon Cytokine Res 1999 Apr
PMID:Serum erythropoietin and interleukin-6 levels in hemodialysis patients with hepatitis virus infection. 1033 88

Thrombocytopenia is a substantial clinical problem for patients with myelodysplastic syndromes (MDS). Cytokine treatment for granulocytopenia and anaemia may further reduce the platelet counts. We studied serum thrombopoietin levels (S-TPO) in 52 patients with MDS and 96 healthy controls and related the results to clinical and morphological variables. S-TPO was also assessed after treatment with granulocyte-CSF (G-CSF) and erythropoietin (EPO) in 30 of these patients. S-TPO in MDS was not a normally distributed variable; mean value was 394 pg/ml, SD +/-831 and median value 123 (12-5000 pg/ml). The controls showed lower S-TPO levels than the patients (median 78 pg/ml, P = 0.003) whereas no differences between the MDS subgroups were observed (P = 0.86). Patients with ringed sideroblastic anaemia (RARS) showed the highest platelet counts and higher S-TPO levels than the controls (P = 0.005). No association between platelet counts and S-TPO levels was found in the patients (P = 0.67). TPO levels were generally low in patients with refractory anaemia with an excess of blasts (RAEB), but very high levels were found in five patients. Patients with a high transfusion need had higher S-TPO levels, whereas bone marrow blast counts, cellularity or megakaryocytes showed no correlation with S-TPO. Patients with 5q- showed lower TPO levels than the other patients, indicating that thrombopoietin is not a mediator of thrombocytosis in these cases. Treatment with G-CSF + EPO significantly reduced the platelet counts (P = 0.0002), but this change was not related to significant changes in S-TPO levels or morphology. Patients with RARS and thrombocytosis who normalized their platelet counts showed a concomitant reduction in S-TPO. This may suggest that the increased platelet counts observed in RARS may be caused by increased S-TPO levels. In conclusion, our study shows that platelet, megakaryocyte and thrombopoietin regulation is rather complex in myelodysplastic syndromes and that spontaneous or induced thrombocytopenia are not usually mirrored by increased S-TPO levels.
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PMID:Spontaneous and cytokine-induced thrombocytopenia in myelodysplastic syndromes: serum thrombopoietin levels and bone marrow morphology. Scandinavian MDS Group, Sweden and Norway. 1055 8


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