Further evidence for lymphokine overproduction in severe aplastic anemia [see comments]

Interferon-gamma (IFN-gamma) and tumor necrosis factor (TNF) are lymphokines with a potent hematopoietic progenitor cell suppressive capacity. In untreated and immunosuppressed patients with severe aplastic anemia (SAA) and in control individuals we measured (a) serum levels of IFN-gamma and TNF and its production by peripheral blood mononuclear cells (PBMNC); (b) serum levels of neopterin, a product that reflects endogenous IFN production; (c) resting and activated lymphocyte subpopulations; and (d) serum levels of soluble interleukin- 2 receptor (IL-2R). Serum levels of IFN and TNF did not differ significantly in untreated and treated SAA patients and control individuals. Spontaneous and phytohemagglutinin-induced production of IFN and TNF by PBMNC, however, were highly increased in both untreated and treated SAA patients. Increased and decreased neopterin serum levels in untreated and treated SAA patients, respectively, suggest modulation of endogenous lymphokine release subsequent to immunosuppression. HLA-DR+ antigen was mainly expressed by CD8 T cells. Circulating numbers of activated (CD4 and CD8) T cells and serum levels of IL-2R were not increased in both untreated and treated SAA patients. The proportion of HLA-DR+ T cells in the PBMNC of untreated SAA patients correlated with the extent of lectin-induced IFN production. Although we were unable to confirm previous reports in SAA on (a) detectable IFN in blood and bone marrow serum, (b) improvement of stem cell growth upon neutralization of endogenous IFN, (c) absolutely increased numbers of circulating activated T cells, and (d) normalization of these abnormalities subsequent to successful immunosuppression, our data clearly support previous reports on abnormal lymphokine production in severe aplastic anemia. Our failure to relate this phenomenon to the severity of disease states, however, further raises doubts on the pathogenetic significance of lymphokine overproduction in SAA.

[1]  R. Ohno,et al.  Effect of recombinant human tumor necrosis factor on the colony growth of human leukemia progenitor cells and normal hematopoietic progenitor cells. , 1987, Blood.

[2]  W. Knapp,et al.  In vitro culture studies of granulocyte/macrophage and erythroid progenitor cells in lymphoproliferative disorders , 1986, Virchows Archiv. B, Cell pathology including molecular pathology.

[3]  M. E. Carver,et al.  Serum-free in vitro bioassay for the detection of tumor necrosis factor. , 1986, Journal of immunological methods.

[4]  D. Williams,et al.  The suppressive influences of human tumor necrosis factors on bone marrow hematopoietic progenitor cells from normal donors and patients with leukemia: synergism of tumor necrosis factor and interferon-gamma. , 1986, Journal of immunology.

[5]  K. Lechner,et al.  INCREASED RATIO OF GRANULOCYTE/MACROPHAGE PROGENITOR CELLS (CFU‐GM) TO MULTILINEAGE PROGENITOR CELLS (CFU‐mix) IN THE PERIPHERAL BLOOD FROM PATIENTS WITH ACUTE NON‐LYMPHOBLASTIC LEUKAEMIA IN VERY EARLY REMISSION , 1986, British journal of haematology.

[6]  E. Neumann,et al.  Myeloid progenitor cells in the peripheral blood of patients with hairy cell leukemia and other "leukemic" lymphoproliferative disorders. , 1986, Leukemia research.

[7]  E. Neumann,et al.  Deficiency of fibrinogen and factor VII following treatment of severe aplastic anaemia with anti-thymocyte globulin and high-dose methylprednisolone. , 2009, Scandinavian journal of haematology.

[8]  D. Nelson,et al.  Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro. , 1985, Journal of immunology.

[9]  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.

[10]  N. Zoumbos,et al.  Immunologic abnormalities in patients receiving multiple blood transfusions. , 1984, Annals of internal medicine.

[11]  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.

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

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

[14]  T. Suda,et al.  Suppression of in Vitro Granulocyte‐Macrophage Colony Formation by the Peripheral Mononuclear Phagocytic Cells of Patients with Idiopathic Aplastic Anaemia , 1981, British journal of haematology.

[15]  T. Suda,et al.  Enhancement of granulocytic colony formation of deletion of phagocytic cells in the bone marrow patients with idiopathic aplastic anemia. , 1980, Experimental hematology.

[16]  A. Gratwohl,et al.  Peripheral Blood Cells from Patients with Aplastic Anaemia in Partial Remission Suppress Growth of their Own Bone Marrow Precursors in Culture , 1980, British journal of haematology.

[17]  J. Adamson,et al.  In vitro tests for distinguishing possible immune-mediated aplastic anemia from transfusion-induced sensitization. , 1980, Blood.

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