Glinical Investigator
Clin Investig (1992) 70:922-926
Original Article
© Springer-Verlag 1992
Granuloeyte colony-stimulating factor treatment in AIDS patients U.R. Hengge, N.H. Brockmeyer, and M. Goos Klinik und Poliklinik f/Jr Dermatologie, Venerologie und Allergologie, Universit/it Essen
Summary. Frequent complications of human immunodeficiency virus infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Reasons for neutropenia resulting from hematopoietic failure are infection of the bone marrow and hematotoxicity of treatment with zidovudine, ganciclovir, sulfonamides, and interferons. Moreover, tumor necrosis factor-e, transforming growth factor-/3 and interferon- 7 have been shown to suppress proliferation of bone marrow cells. Both granulocyte (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and ameliorate phagocytic and bactericidic function of neutrophils. We report eight cases of AIDS patients with serious infections and neutropenia ( < 750 cells/gl), who were treated concomitantly with recombinant human GCSF ( 3 4 gg subcutaneously per kilogram body weight daily). G-CSF treatment was well tolerated in all patients and showed no side effects or disturbances of other lineages than neutrophils. Lifethreatening bacterial infections were treated successfully by stimulating the neutrophil immune system. This therapy shortened the duration of subsequent treatment with antibiotics. Since human immunodeficiency virus infects CD4-positive monocytes and macrophages, which are stimulated by GM-CSF, G-CSF seems to be the cytokine of choice, if stimulation of the neutrophil lineage is warranted. Key words: A I D S - Granulocyte colony-stimulat-
ing factor - Neutropenia
Frequent complications of human immunodeficiency virus (HIV) infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Besides anemia which occurs during the disease []3], neutropenia often threatens patients' lives. Abbreviations: G-CSF = granulocyte colony-stimulating factor;
GM-CSF=granulocyte-macrophage colony-stimulating factor; HIV = human immunodeficiency virus
Neutropenia may result from hematopoietic failure due to infection of the bone marrow by atypical mycobacteria and cytomegalovirus. HIV itself is not likely to cause cytopenia; hematopoietic progenitor cells are infrequently infected by HIV in vivo [6, 21]. Defects in the proliferative capacity of progenitor cells [26], inhibition of growth by 76 T-cell receptor-positive lymphocytes [9], and increased destruction of mature neutrophils by autoantibodies have been described [16]. Tumor necrosis factor-e, transforming growth factor-/~ and interferon-? have also been shown to suppress proliferation of bone marrow cells [2, 8]; moreover, various drugs (zidovudine, ganciclovir, sulfonamides, and interferons) affect blood cell production [14]. Both granulocyte (G-CSF) and granulocytemacrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and enhance their phagocytic and bactericidal functions [17, 23-25]. The risk of a bacterial infection increases with the severity and duration of neutropenia. G-CSF has been shown to prevent and shorten infections in a randomized placebo-controlled trial in patients with chemotherapy-induced neutropenia [5] and to reduce hospitalization [1]. Clinical studies with GM-CSF [10] or G-CSF combined with erythropoietin in HIV patients have been carried out to reduce hematotoxic effects of zidovudine treatment [201. We report here eight cases of AIDS patients with serious infections and neutropenia (
Clin Investig (1992) 70:922-926
Original Article
© Springer-Verlag 1992
Granuloeyte colony-stimulating factor treatment in AIDS patients U.R. Hengge, N.H. Brockmeyer, and M. Goos Klinik und Poliklinik f/Jr Dermatologie, Venerologie und Allergologie, Universit/it Essen
Summary. Frequent complications of human immunodeficiency virus infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Reasons for neutropenia resulting from hematopoietic failure are infection of the bone marrow and hematotoxicity of treatment with zidovudine, ganciclovir, sulfonamides, and interferons. Moreover, tumor necrosis factor-e, transforming growth factor-/3 and interferon- 7 have been shown to suppress proliferation of bone marrow cells. Both granulocyte (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and ameliorate phagocytic and bactericidic function of neutrophils. We report eight cases of AIDS patients with serious infections and neutropenia ( < 750 cells/gl), who were treated concomitantly with recombinant human GCSF ( 3 4 gg subcutaneously per kilogram body weight daily). G-CSF treatment was well tolerated in all patients and showed no side effects or disturbances of other lineages than neutrophils. Lifethreatening bacterial infections were treated successfully by stimulating the neutrophil immune system. This therapy shortened the duration of subsequent treatment with antibiotics. Since human immunodeficiency virus infects CD4-positive monocytes and macrophages, which are stimulated by GM-CSF, G-CSF seems to be the cytokine of choice, if stimulation of the neutrophil lineage is warranted. Key words: A I D S - Granulocyte colony-stimulat-
ing factor - Neutropenia
Frequent complications of human immunodeficiency virus (HIV) infection are hematopoietic failure and poor tolerance of myelosuppressive drugs. Besides anemia which occurs during the disease []3], neutropenia often threatens patients' lives. Abbreviations: G-CSF = granulocyte colony-stimulating factor;
GM-CSF=granulocyte-macrophage colony-stimulating factor; HIV = human immunodeficiency virus
Neutropenia may result from hematopoietic failure due to infection of the bone marrow by atypical mycobacteria and cytomegalovirus. HIV itself is not likely to cause cytopenia; hematopoietic progenitor cells are infrequently infected by HIV in vivo [6, 21]. Defects in the proliferative capacity of progenitor cells [26], inhibition of growth by 76 T-cell receptor-positive lymphocytes [9], and increased destruction of mature neutrophils by autoantibodies have been described [16]. Tumor necrosis factor-e, transforming growth factor-/~ and interferon-? have also been shown to suppress proliferation of bone marrow cells [2, 8]; moreover, various drugs (zidovudine, ganciclovir, sulfonamides, and interferons) affect blood cell production [14]. Both granulocyte (G-CSF) and granulocytemacrophage colony-stimulating factor (GM-CSF) increase neutrophil counts and enhance their phagocytic and bactericidal functions [17, 23-25]. The risk of a bacterial infection increases with the severity and duration of neutropenia. G-CSF has been shown to prevent and shorten infections in a randomized placebo-controlled trial in patients with chemotherapy-induced neutropenia [5] and to reduce hospitalization [1]. Clinical studies with GM-CSF [10] or G-CSF combined with erythropoietin in HIV patients have been carried out to reduce hematotoxic effects of zidovudine treatment [201. We report here eight cases of AIDS patients with serious infections and neutropenia (
