Gamma-interferon in aplastic anemia: inability to detect significant levels in sera or demonstrate hematopoietic suppressing activity

A radioimmunoassay (RIA) was used to quantitate biologically active gamma interferon (INF-gamma) in sera and in supernatants of cultured mononuclear cells obtained from 50 patients with aplastic anemia. Only five of the 50 serum samples had INF-gamma levels above background (greater than 0 less than 0.5 units per mL). Detectable levels of spontaneous INF-gamma (0.3 to 868 U/mL) were found in 18 of the 50 mononuclear cell supernatants tested. The addition of patient sera or INF-gamma positive supernatants to cultures of normal hematopoietic colonies did not result in reduced colony growth. Flow cytofluorimetric analysis of mononuclear cells failed to establish a correlation between the presence of INF-gamma in supernatants and the number of activated T cells or natural killer (NK) cells in the mononuclear cell population. However, a significant correlation did exist between the presence of monocytes and the production of INF-gamma. Contrary to previous reports, our data suggest that patients with aplastic anemia do not have high circulating levels of INF-gamma. Unstimulated mononuclear cells from some patients will produce significant levels of INF-gamma, but this does not result in decreased in vitro hematopoiesis.

[1]  R. Shadduck,et al.  Interferon‐induced aplasia: Evidence for t‐cell‐mediated suppression of hematopoiesis and recovery after treatment with horse antihuman thymocyte globulin , 1985, American journal of hematology.

[2]  R. Storb,et al.  Subsets of patients with aplastic anemia identified by flow microfluorometry. , 1985, The New England journal of medicine.

[3]  G. Trinchieri,et al.  Immune interferon: a pleiotropic lymphokine with multiple effects. , 1985, Immunology today.

[4]  N. Young,et al.  Circulating activated suppressor T lymphocytes in aplastic anemia. , 1985, The New England journal of medicine.

[5]  N. Young,et al.  Interferon is a mediator of hematopoietic suppression in aplastic anemia in vitro and possibly in vivo. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[6]  G. Trinchieri,et al.  Response of resting human peripheral blood natural killer cells to interleukin 2 , 1984, The Journal of experimental medicine.

[7]  J. Vilček,et al.  Use of monoclonal antibodies as sensitive and specific probes for biologically active human gamma-interferon. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[8]  N. Young,et al.  Interferon is the suppressor of hematopoiesis generated by stimulated lymphocytes in vitro. , 1984, Journal of immunology.

[9]  R. Storb,et al.  Acquired severe aplastic anemia: progress and perplexity. , 1984, Blood.

[10]  J. Vilček,et al.  Natural and recombinant Escherichia coli-derived interferon-gamma differ in their reactivity with monoclonal antibody. , 1984, Journal of immunology.

[11]  B. Aggarwal,et al.  Interrelationships of human interferon-gamma with lymphotoxin and monocyte cytotoxin , 1984, The Journal of experimental medicine.

[12]  B. Torok-Storb,et al.  Correlation of two in vitro tests with clinical response to immunosuppressive therapy in 54 patients with severe aplastic anemia. , 1984, Blood.

[13]  S. Matis,et al.  Natural killer cells suppress human erythroid stem cell proliferation in vitro. , 1984, Blood.

[14]  R. Storb,et al.  Therapy of severe aplastic anemia with anti-human thymocyte globulin and androgens: the effect of HLA-haploidentical marrow infusion. , 1984, Blood.

[15]  T. Yokochi,et al.  Human B Cell and B Cell Blast-Associated Surface Molecules Defined with Monoclonal Antibodies , 1984 .

[16]  E. Gluckman,et al.  Immunosuppressive treatment of aplastic anemia as an alternative treatment for bone marrow transplantation. , 1984, Seminars in hematology.

[17]  R. Neerhout,et al.  T-lymphocyte--mediated granulopoietic failure. In vitro identification of prednisone-responsive patients. , 1983, The New England journal of medicine.

[18]  G. Hale,et al.  Removal of T cells from bone marrow for transplantation: a monoclonal antilymphocyte antibody that fixes human complement. , 1983, Blood.

[19]  R. Storb,et al.  Antithoracic duct lymphocyte globulin therapy of severe aplastic anemia. , 1983, Blood.

[20]  L. Juliano,et al.  Comparative analysis of the influences of human gamma, alpha and beta interferons on human multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells. , 1983, Journal of immunology.

[21]  D. Weigent,et al.  Recombinant gamma interferon enhances natural killer cell activity similar to natural gamma interferon. , 1983, Biochemical and biophysical research communications.

[22]  J. Phillips,et al.  NKP-15: a monoclonal antibody reactive against purified human natural killer cells and granulocytes. , 1983, Immunology letters.

[23]  R. Champlin,et al.  Antithymocyte globulin treatment in patients with aplastic anemia: a prospective randomized trial. , 1983, The New England journal of medicine.

[24]  G. Chikkappa,et al.  T gamma (T gamma) cells suppress growth of erythroid colony-forming units in vitro in the pure red cell aplasia of B-cell chronic lymphocytic leukemia. , 1982, The Journal of clinical investigation.

[25]  Neumann Ha,et al.  Effect of interferon on pluripotent hemopoietic progenitors (CFU-GEMM) derived from human bone marrow. , 1982 .

[26]  B. Askonas,et al.  Immune interferon release when a cloned cytotoxic T-cell line meets its correct influenza-infected target cell , 1982, Nature.

[27]  C. Balch,et al.  A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). , 1981, Journal of immunology.

[28]  A. Gratwohl,et al.  Treatment of severe aplastic anaemia with antilymphocyte globulin or bone-marrow transplantation. , 1981, British medical journal.

[29]  B. Rabin,et al.  Aplastic anemia following infectious mononucleosis: possible immune etiology. , 1979, Experimental hematology.

[30]  T. Merigan,et al.  Suppressive effect of interferon on erythroid cell proliferation. , 1979, Experimental hematology.

[31]  A. Bacigalupo,et al.  Bolus methylprednisolone in severe aplastic anemia. , 1979, The New England journal of medicine.

[32]  J. Gutterman,et al.  Human leukocyte interferon preparation blocks granulopoietic differentiation. , 1979, Blood.

[33]  N. Abdou,et al.  Aplastic anemia associated with bone marrow suppressor T‐Cell hyperactivity: Successful treatment with antithymocyte globulin , 1978, American journal of hematology.

[34]  J. Finke,et al.  Case report. Aplastic anemia. Effect of antithymocyte globulin on erythroid colony formation. , 1978, Cleveland Clinic quarterly.

[35]  R. Good,et al.  Aplastic anaemia: Evidence for an immunological mechanism. , 1976, Lancet.

[36]  J. Youngner,et al.  Production and properties of migration inhibitory factor and interferon in the circulation of mice with delayed hypersensitivity. , 1973, Journal of immunology.