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)

The possible role of antibody and T-lymphocytes was investigated in the pure red cell aplasia (PRCA) associated with feline leukemia virus, subgroup C (FeLV-C), infection. In previous studies, erythroid colony-forming cells were undetectable in marrow culture of cats with PRCA. Yet erythroid burst-forming cells (BFU-E) remained, suggesting that BFU-E were able to differentiate in vitro but not in vivo. It was inferred that immunologic suppression may contribute to the pathogenesis of feline PRCA, and the interactions of antibody and T-lymphocytes with erythroid and granulocyte-macrophage progenitors were studied. Incubation of normal or PRCA marrow cells with PRCA serum or IgG concentrated from this serum and then complement (C') failed to decrease hematopoietic colony growth when compared to the results obtained with cultures of marrow cells incubated with C' alone. In crossover coculture studies, T-cells from Safari cats with PRCA had no inhibitory effect on colony growth from normal or autologous PRCA marrow cells. For the determination of whether feline PRCAs were associated with a clonal T-cell process, lymphocytes were obtained periodically from glucose-6-phosphate dehydrogenase (Glc-6-PD) heterozygous cats following FeLV-C infection and were expanded with a crude preparation of interleukin-2. The ratios of Glc-6-PD enzyme types in these samples did not change as cats developed anemia, suggesting that the inhibition of erythropoiesis was not associated with the clonal expansion of T-cells. These studies, therefore, do not support the premise that feline PRCA results from the interaction of antibody or T-cells with erythroid progenitors.
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PMID:Lymphocytes and antibody in retrovirus-induced feline pure red cell aplasia. 302

The role of immunocompetent cells in hemopoiesis remains controversial. We used an autologous system in which activated peripheral blood mononuclear cells (LAK) and interleukin-2 (IL-2) are administered to patients with cancer. We found little change in the numbers of circulating erythroid progenitors. Cocultures of these progenitors with LAK or supernatants lead to a decrease in the numbers of detectable burst forming units-erythroid (BFU-E) in culture. However, using an assay for burst promoting activity (BPA) we noted production of this hemopoietin by these LAK cells. We could not detect circulating levels of gamma interferon (IF). Variable levels were found in the LAK supernatants. We could not detect circulating eosinophil progenitors (CFU-Eo), but we did find evidence of production of a colony stimulating factor (CSF), which gave rise to a high number of eosinophil colonies in cultures of bone marrow. These results suggest that administration of LAK/IL-2 has potent effects on hemopoiesis and that these effects may emphasize the anemia and eosinophilia seen in patients receiving this therapy.
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PMID:Cellular interactions in hemopoiesis. 311 39

Interleukin-2 (IL-2) is a chemically defined lymphokine (LK) available as mixed human (LK) preparations, as partially purified lymphoblastoid IL-2, or as recombinant human IL-2. Each has different actions dependent on companion LKs showing synergistic interaction (e.g., IL-1 and gamma-interferon (gamma-IFN]). IL-2 acts to expand activated T cells; to activate natural killer (NK) cells, lymphokine-activated killer (LAK) cells, and cytolytic T cells (CTL); to regulate T-cell ontogeny via actions on prothymocytes and immature T cells; and to induce gamma-IFN and activate tumoricidal macrophages. IL-2 acts via specific cell surface receptors on protein kinase C and cyclic GMP-related mechanisms. While stable, its in vivo half-life is short and its persistence is important for it to induce a response. Toxicities include an influenzia-like syndrome, anemia, eosinophilia, and fluid accumulation. In vivo actions include augmentation of cytotoxic responses at high doses, T-cell adjuvant actions, and T-cell restorative actions at midrange doses and at low doses with companion LKs. Antitumor responses in man and animals occur, but irregularly. They are maximized by the concomitant use of LAK cells, cytoreductive therapy, antisuppressor cell therapy, and regional or persistent administration. IL-2 offers hope for more effective therapy of cancer and a variety of immunodeficiency diseases involving IL-2 defects, including AIDS, viral infections, and autoimmune diseases.
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PMID:Recent advances in the preclinical and clinical immunopharmacology of interleukin-2: emphasis on IL-2 as an immunorestorative agent. 314 Oct 54

Interleukin-2 (IL-2) is a 15,000 dalton glycoprotein produced naturally by human T-cells during an immune response. IL-2 has been demonstrated to have substantial activity alone or in combination with the adoptive transfer of lymphokine-activated killer cells in murine tumor models. IL-2 derived from both natural (Jurkat human T-cell tumor) and recombinant (Escherichia coli) sources has been studied in Phase I protocols designed to evaluate toxicity in patients with a variety of solid tumors and to ascertain improvement in clinical parameters and immunologic status. A total of 16 patients (7 with acquired immune deficiency syndrome [AIDS] and 9 with non-AIDS malignancies) were treated with Jurkat derived IL-2. The total maximum dose (1.3 X 10(5) U/kg) was limited only by supply of this reagent. A total of 25 patients have been treated with recombinant IL-2 (RIL-2) alone. Dose-limiting toxicity manifested by marked malaise and weight gain was achieved with doses of RIL-2 of 10(6) U/kg as a single bolus or 3000 U/kg/hr. IL-2 could be administered intraperitoneally with similar toxicity. Minimal renal or hepatic toxicity was demonstrated. Hematologic toxicity was limited to mild anemia (25/25), thrombocytopenia (10/25), and marked reversible eosinophilia (15/25). Pronounced weight gain greater than 2 kg (16/25) occurred in most patients, primarily those who received cumulative doses of greater than 1-3 X 10(5) U/kg of IL-2. The weight gain amounted to as much as 10% to 20% of the pretreatment weight over 3 weeks of treatment and limited our ability to give higher doses. Two partial responses (greater than 50% decrease in cross sectional diameters) were seen in two patients with melanoma metastatic to the lung.
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PMID:Clinical effects and toxicity of interleukin-2 in patients with cancer. 349 Sep 3

In order to evaluate the efficacy of dexamethasone (dex) in reducing the toxicity of therapy with lymphokine-activated killer (LAK) cells and interleukin-2 (IL-2), we treated six patients receiving this form of immunotherapy with intravenous (IV) dex, 4 mg every six hours. Compared with a control group of 27 patients not receiving dex with their immunotherapy, these corticosteroid-treated patients were able to tolerate the administration of more IL-2, yet experienced significantly less toxicity. Dyspnea, confusion, fever, mean peak serum creatinine, and bilirubin levels during treatment were significantly reduced in corticosteroid-treated patients, with a corresponding decrease in pruritus in this group as well. Overall weight gain was not different between groups, although a curtailment of weight gain temporally related to dex treatment was seen in some patients. Hematologic side effects, including anemia, eosinophilia, and thrombocytopenia, were not reduced by dex. These results suggest that dex can inhibit at least some of the toxic side effects of LAK cell and IL-2 therapy. Because of the concern that the therapeutic effect may also be abrogated, future studies combining corticosteroids with this form of immunotherapy should be undertaken with caution.
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PMID:Reduction of toxicity of interleukin-2 and lymphokine-activated killer cells in humans by the administration of corticosteroids. 349 32

Immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells generated from autologous lymphocytes has produced significant tumor regressions in patients with advanced cancer. In the current study, we reviewed the hematologic effects associated with this therapy in our initial 42 patients. Eighty-eight percent of the treated patients developed anemia that required greater than or equal to 4 units of red cell transfusions, and 43% received at least 8 units. Only a blood loss of 2 to 3 units could be attributed to repeated phlebotomy, cytophereses, and hemodilution. IL-2 administration also resulted in thrombocytopenia as well as lymphopenia and eosinophilia. Forty-three percent of patients developed platelet counts of less than or equal to 50,000/microL, and 36% of the total group required platelet transfusions. Mild neutropenia and a rebound lymphocytosis followed discontinuation of IL-2 treatment. To explore the possible mechanisms for these hematologic effects, standard hematopoietic colony assays were conducted on serial blood samples from five patients. IL-2 produced a significant decline in circulating erythroid (BFU-E) and granulocytic/macrophage (CFU-C) progenitors, which rebounded after the discontinuation of IL-2 therapy. Infusion of IL-2 also resulted in measurable serum levels of gamma-interferon. Some of the hematologic effects of immunotherapy with LAK cells and IL-2 may be the result of IL-2-mediated suppression of hematopoiesis.
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PMID:Hematologic effects of immunotherapy with lymphokine-activated killer cells and recombinant interleukin-2 in cancer patients. 349 2

The authors have studied the case of a female patient with rheumatoid polyarthritis, who developed a lymphocytic proliferation in the blood, the marrow, and the liver, associated with a neutropenia. Several similar cases have been recently reported in the literature. The cellular proliferation is made of large granulous lymphocytes and the study of membrane markers enables to find the following homogeneous phenotype: E rosette+, CD8+, HNK-1+, FcR+, CD4-luminal diameter "divided by degrees - -, IgS-, HLA class II-. This lymphocytic sub-population produces little interleukin-2, responds weakly to mitogens (PHA, CON A, PWM), and inhibits the response of normal lymphocytes to the same mitogens. These lymphocytes have a weak natural killer activity but, on the contrary, develop a very strong cytotoxic activity which is antibody-dependent. Clinically, splenomegaly, anemia and infections are frequent and hepatomegaly or thrombopenia more rare. Adenopathies are never present. The evolution is chronic in nature and not very aggressive, although the lymphocytic proliferation is monoclonal in origin, as demonstrated in molecular biology studies. The neutropenia might be secondary to an inhibiting effect of lymphocytes on the granular precursors of the bone marrow. There is a definite association between this lympho-proliferative syndrome and rheumatoid polyarthritis, and this association appears to be different from the Felty's syndrome.
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PMID:[Characterization of chronic lymphocytic proliferation in a female patient having rheumatoid polyarthritis with neutropenia]. 361 55

The activity capable of promoting the growth of human erythroid burst-forming cells (BFU-E) in culture was measured in the sera from 39 patients with aplastic anemia (AA) and compared with similar activity in patients with various other hematologic disorders and 31 normal subjects. Burst-promoting activity (BPA) was determined by its ability to support erythroid burst growth from adherent cell-depleted normal human marrow cells. The results were expressed as the percentage of burst growth supported by test serum compared with cultures established in the presence of 20% test serum and 2.5% phytohemagglutinin-stimulated lymphocyte conditioned medium. The mean BPA level in normal serum was 18.5% (1.5 +/- SEM) and was not significantly different from BPA levels in patients with various forms of nonhypoplastic anemia or polycythemia (10.2% +/- 1.2%). In contrast, 15 of the 39 patients with AA had elevated BPA levels, ranging from 40.0% to 106.0%. These elevated levels did not correlate with serum erythropoietin or hematocrit values, white blood cell count, platelet count, time from diagnosis, or the presence or numbers of BFU-E in circulation. The BPA was shown not to be T cell growth factor (interleukin-2), and the effect was not blocked by the addition of cyclosporine to culture, consistent with a direct effect of this activity on BFU-E. When the 39 patients with AA were treated with antithymocyte globulin, 20 obtained a complete or partial remission. BPA levels determined from sera obtained before treatment did not correlate with response or duration of survival but did correlate with granulocyte-macrophage colony-stimulating activity (GM-CSA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hematopoietic growth factors in human serum. erythroid burst-promoting activity in normal subjects and in patients with severe aplastic anemia. 404 96

Interleukin-2 (IL-2)-deficient (IL-2-/-) mice develop anemia and colonic inflammatory bowel disease. To elucidate the mechanism of this disease, we have bred IL-2-/- mice to two strains of immunodeficient mice, RAG-2-deficient (RAG-2-/-, lacking B and T cells) and JH-deficient mice (JH-/-, lacking B cells). IL-2-/-, RAG-2-/- double-mutant mice are disease free, while IL-2-/-, JH-/- double-mutant mice succumb to bowel disease at the same rate as IL-2-/- littermates. IL-2-/-, JH-/- mice do not, however, succumb to anemia. Thus, spontaneous intestinal inflammation in IL-2-/- mice requires mature T cells, not B cells, while anemia is dependent on B cells.
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PMID:T cells, but not B cells, are required for bowel inflammation in interleukin 2-deficient mice. 759 26

A phase II multiinstitutional clinical trial was conducted to evaluate the safety and efficacy of the subcutaneous outpatient administration of recombinant human interleukin-2 and alpha-interferon in patients with progressive metastatic renal cell carcinoma. One hundred and forty-five patients were entered on this study between October 1989 and May 1991. Among 134 patients evaluable for treatment response, there were six complete (4.5%) and twenty partial (14.9%) responders, with an overall response rate of 19.4% (95% confidence interval, 13-26%). The median duration of complete remissions was 228 (range 51(+)-520+) days; the median duration of partial tumor regressions was calculated at 226 (range 112-473+) days. The overall median survival from start of therapy was 14.2 (range 1-23+) months. Fever, chills and general fatigue occurred in the majority of patients treated and were measured at grade II, III and IV in up to 55%, 24% and 3% of all evaluable patients, respectively. Three patients each developed grade III hypotension, dyspnea and diarrhea; two patients each had grade III and grade IV elevations of alkaline phosphatase; two and one patients respectively, exhibited grade III anemia and grade IV thrombocytopenia; two patients experienced severe cutaneous toxicity. The majority of patients received treatment in the outpatient setting. In summary, the outpatient use of subcutaneous interleukin-2 and alpha-interferon was effective in patients with advanced metastatic renal cell carcinoma; it was associated with less toxicity and thus, could improve the therapeutic index of interleukin-2 based biologic therapy when compared against high dose intravenous therapy.
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PMID:Subcutaneous recombinant interleukin-2 and alpha-interferon in patients with advanced renal cell carcinoma: results of a multicenter Phase II Study. 780 70


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