title: Bone marrow fibroblasts from children with aplastic anemia exhibit reduced interleukin-6 production in response to cytokines and viral challenge.
abstract: Defects of the bone marrow microenvironment have been implicated in the pathogenesis of aplastic anemia (AA). We examined granulocyte/macrophage colony-stimulating factor (GM-CSF) and IL-6 production in bone marrow fibroblasts from five children with AA in response to cytokines and viral challenge with cytomegalovirus (CMV). Cytokine-stimulated IL-6 production in patients' fibroblasts was significantly reduced, whereas GM-CSF production was found to be comparable to normal controls. Also, CMV-mediated stimulation of IL-6 production was significantly lower in bone marrow fibroblasts from patients with AA. During the late phase of CMV-infection, IL-6 production was suppressed in CMV-infected fibroblasts from patients with AA with 90% inhibition of IL-6 protein production and marked reduction in IL-6 mRNA accumulation. Defective IL-6 production in bone marrow fibroblasts might contribute to hematopoietic suppression in some patients with AA.
authors.affiliation: Department of Pediatric Haematology/Oncology, Heinrich-Heine University Medical Center, Düsseldorf, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Dilloo
authors.forename: R
authors.initials: R
authors.lastname: Vöhringer
authors.forename: A
authors.initials: A
authors.lastname: Josting
authors.forename: K
authors.initials: K
authors.lastname: Habersang
authors.forename: A
authors.initials: A
authors.lastname: Scheidt
authors.forename: S
authors.initials: S
authors.lastname: Burdach
mesh_terms: D000293:Adolescent; D000741:Anemia, Aplastic / Q000276:immunology*; D001483:Base Sequence; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000276:immunology*; D003587:Cytomegalovirus / Q000276:immunology*; D005199:Fanconi Anemia / Q000276:immunology*; D005347:Fibroblasts / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D016207:Cytokines; D015850:Interleukin-6; D012333:RNA, Messenger; D016178:Granulocyte-Macrophage Colony-Stimulating Factor