Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood. I. Comparison with isolated PBMC stimulation.

in Cytokine (1992), 4(3), 239-48

Production of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), interferon gamma (IFN-gamma) and granulocyte-macrophage colony ... [more ▼]

Production of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after stimulation by lipopolysaccharide (LPS) and phytohemagglutinin (PHA) was studied in 1/10 diluted whole blood (WB) culture and in peripheral blood mononuclear cell (PBMC) culture. Cytokines IL-1 beta, TNF-alpha and IL-6 are preferentially stimulated by LPS whereas IL-2, IFN-gamma and GM-CSF are stimulated by PHA. Combination of 5 micrograms/ml PHA and 25 micrograms/ml LPS gave the most reliable production of the six cytokines studied. IL-1 beta, TNF-alpha and IL-6 represent a homogeneous group of early-produced cytokines positively correlated among themselves and with the number of monocytes in the culture (LeuM3). Furthermore, IL-1 beta was negatively correlated with the number of T8 lymphocytes. IL-2, IFN-gamma and GM-CSF represent a group of late-produced cytokines. Kinetics and production levels of IL-6 and GM-CSF are similar in WB and PBMC cultures. In contrast, production levels of TNF-alpha and IFN-gamma are higher in WB than in PBMC whereas production levels of IL-6 and IL-2 are lower in WB than in PBMC. Individual variation in responses to PHA + LPS was always higher in PBMC cultures than in WB cultures. The capacity of cytokine production in relation to the number of mononuclear cells is higher in WB, or in PBMC having the same mononuclear cell concentration as WB, than in conventional cultures of concentrated PBMC (10(6)/ml). Because it mimics the natural environment, diluted WB culture may be the most appropriate milieu in which to study cytokine production in vitro. [less ▲]

Evaluation of erythroid marrow response to recombinant human erythropoietin in patients with cancer anaemia.

in Haematologica (1992), 77(6), 494-501

BACKGROUND. Anaemia is a frequent finding in patients with cancer and may be due to different causes, including blunted erythropoietin production. MATERIALS AND METHODS. In a pilot study, we administered ... [more ▼]

BACKGROUND. Anaemia is a frequent finding in patients with cancer and may be due to different causes, including blunted erythropoietin production. MATERIALS AND METHODS. In a pilot study, we administered recombinant human erythropoietin (rHuEPO) to twelve patients with solid tumours and secondary anaemia. rHuEPO was given subcutaneously 5 d per week at escalating doses (75 to 150 U/kg per day): the aim of treatment was a Hb level > or = 10 g/dl without blood transfusion. We evaluated endogenous EPO production through serum EPO levels and erythroid marrow activity by means of serum transferrin receptor (TfR). RESULTS. Six out of 12 subjects had defective endogenous EPO production. All patients but two responded to treatment with steady increases in Hb levels above 10 g/dl, and the median dose of rHuEPO required for correction of anaemia was 75 U/kg. Response was associated with an early increase in serum TfR. Six patients developed functional iron deficiency and required iron supplementation to obtain response. Treatment improved functional ability in 4/10 responders. CONCLUSIONS. Subcutaneous rHuEPO can stimulate erythroid marrow activity in cancer anaemia, even in patients with advanced disease, and marrow response can be adequately monitored by serum TfR. Functional iron deficiency as a cause of nonresponse to rHuEPO is frequent in these patients and may require parenteral iron administration. Although erythropoietin can improve the anaemia of cancer, the decision to treat should be individualised for each patient, looking more at the quality of life and cost-effectiveness than at cosmetic increases in the haemoglobin level. [less ▲]

Serum erythropoietin levels during haematinic treatment

in British Journal of Haematology (1992), 82

Le dosage du récepteur circulant de la transferringe : une nouveauté pour quantifier l'érythropoïèse

in Médecine et Hygiène (1991), 49

Les échanges de fer entre les tissus se font par l'intermédiaire de la transferrine plasmatique qui donne son fer aux cellules grâce à son interaction avec un récepteur mambranaire spécifique. Une forme ... [more ▼]

Les échanges de fer entre les tissus se font par l'intermédiaire de la transferrine plasmatique qui donne son fer aux cellules grâce à son interaction avec un récepteur mambranaire spécifique. Une forme soluble du récepteur de la transferrine a été mise en évidence dans le sang. Son dosage par méthode ELISA représente une excellente mesure quantitative de l'érythropoïèse qui devrait remplacer les méthodes anciennes moins fiables (réticulocytes) et plus complexes (tests au fer marqué). [less ▲]

Circulating erythropoietin levels after bone marrow transplantation: inappropriate response to anemia in allogeneic transplants.

in Blood (1991), 77(4), 868-73

We studied 24 recipients of autologous bone marrow transplantation (ABMT) or allogeneic BMT (BMT) to determine whether impaired erythropoietin (Epo) response to anemia could delay full erythropoietic ... [more ▼]

We studied 24 recipients of autologous bone marrow transplantation (ABMT) or allogeneic BMT (BMT) to determine whether impaired erythropoietin (Epo) response to anemia could delay full erythropoietic recovery. Observed Epo levels were compared with predicted levels based on the relationship between Epo and hematocrit in 125 control subjects. Circulating Epo levels were normal during conditioning and the early posttransplant period. Between days 21 and 180, Epo levels remained normal in ABMT patients but were inappropriately low for the degree of anemia in BMT patients. Median time to full erythropoietic engraftment was longer in BMT than in ABMT recipients. Circulating Epo returned to appropriate levels after day 180, except in patients with active cytomegalovirus infection. We conclude that impaired Epo response to anemia can contribute to delayed erythropoietic recovery after allogenic BMT. Renal toxicity of ciclosporin, interaction between host and donor marrow, and cytomegalovirus infection might play a role. This study could support the use of recombinant human Epo to accelerate erythropoietic engraftment after BMT. [less ▲]

Relationship of serum selenium to tumor activity in acute non lymphocytic leukemia (ANLL) and chronic lymohocytic leukemia (CLL)

in Metal Ions in Biology and Medicine (1990)

Allogreffes et autogreffes de moelle osseuse. Indications, résultats, perspectives

in Médecine et Hygiène (1990), 48

This paper presents a brief overview of bone marrow transplantation including pretransplant considerations, the transplant procedure, early and delayed complications and the relative roles of chemotherapy ... [more ▼]

This paper presents a brief overview of bone marrow transplantation including pretransplant considerations, the transplant procedure, early and delayed complications and the relative roles of chemotherapy versus transplantation in leukemias and lymphomias. [less ▲]

Intact transferrin receptors in human plasma and their relation to erythropoiesis.

in Blood (1990), 75(1), 102-7

Intact transferrin receptor molecules complexed with transferrin were found in human plasma. The concentration of receptors was determined by an enzyme-linked immunosorbent assay that uses polyclonal ... [more ▼]

Intact transferrin receptor molecules complexed with transferrin were found in human plasma. The concentration of receptors was determined by an enzyme-linked immunosorbent assay that uses polyclonal antibodies. The mean concentration of 8,279 micrograms/L in 56 normal adults appears to be unrelated to age or sex. Additional receptor measurements were performed on plasmas from 260 subjects with erythropoietic disorders. Decreased concentration of plasma receptors was found in patients with erythroid hypoplasia and increased numbers in those with erythroid hyperplasia. Ferrokinetic measurements of erythropoiesis were compared with numbers of receptors in 148 subjects, and a close correlation was found (r = .86). Both sets of values, measured in different conditions and expressed in relation to normal, were consistent with expected values. Receptor values were unproportionally increased only in conditions of iron deficiency. It is concluded that plasma receptors have a constant relationship to tissue receptors, and their number in most instances reflects the rate of erythropoiesis. [less ▲]

Erythropoietine: utilisation diagnostique et therapeutique.

in Revue Médicale de Liège (1990), 45(6), 261-7

Relationship of Serum Selenium Levels to Tumor Activity in Acute Non-Lymphocytic Leukemia

in Carcinogenesis (1989), 10(11), 2089-91

Serum selenium (Se) levels were measured before, during and after high-dose induction chemotherapy in 70 patients with acute non-lymphocytic leukemia (ANLL). Pre-treatment serum Se levels were lower in ... [more ▼]

Serum selenium (Se) levels were measured before, during and after high-dose induction chemotherapy in 70 patients with acute non-lymphocytic leukemia (ANLL). Pre-treatment serum Se levels were lower in patients than in controls (0.082 +/- 0.033 micrograms/ml versus 0.097 +/- 0.035 micrograms/ml, P less than 0.01). Pretreatment serum Se correlated inversely with the absolute peripheral blast cell count (R = -0.62, P less than 0.001) and other measurements of the tumor burden. Seven days after the initiation of chemotherapy, serum Se increased significantly in proportion to the initial tumor burden (P less than 0.01). Thereafter, serum Se levels remained essentially normal in patients entering a complete remission while decreasing gradually in failures. In conclusion, these data do not lend support to the hypothesis that a low selenium status enhances the risk of developing ANLL, but indicate that serum Se levels in patients with acute leukemia are mostly dependent on tumor activity. [less ▲]