title: Cytokine production by bone marrow mononuclear cells in inherited bone marrow failure syndromes.
abstract: Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anaemia (DBA), and Shwachman-Diamond syndrome (SDS) are characterized by the progressive development of bone marrow failure. Overproduction of tumour necrosis factor-α (TNF-α) from activated bone marrow T-cells has been proposed as a mechanism of FA-related aplasia. Whether such overproduction occurs in the other syndromes is unknown. We conducted a comparative study on bone marrow mononuclear cells to examine the cellular subset composition and cytokine production. We found lower proportions of haematopoietic stem cells in FA, DC, and SDS, and a lower proportion of monocytes in FA, DC, and DBA compared with controls. The T- and B-lymphocyte proportions were similar to controls, except for low B-cells in DC. We did not observe overproduction of TNF-α or IFN-γ by T-cells in any patients. Induction levels of TNF-α, interleukin (IL)-6, IL-1β, IL-10, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor in monocytes stimulated with high-dose lipopolysaccharide (LPS) were similar at 4 h but lower at 24 h when compared to controls. Unexpectedly, patient samples showed a trend toward higher cytokine level in response to low-dose (0·001 μg/ml) LPS. Increased sensitivity to LPS may have clinical implications and could contribute to the development of pancytopenia by creating a chronic subclinical inflammatory micro-environment in the bone marrow.
authors.affiliation: Human Papillomavirus Immunology Laboratory, Science Applications International Corporation (SAIC)-Frederick, Incorporated, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
authors.forename: Ken
authors.initials: K
authors.lastname: Matsui
authors.forename: Neelam
authors.initials: N
authors.lastname: Giri
authors.forename: Blanche P
authors.initials: BP
authors.lastname: Alter
authors.forename: Ligia A
authors.initials: LA
authors.lastname: Pinto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism*; D001855:Bone Marrow Diseases; D000080983:Bone Marrow Failure Disorders; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D006457:Hemoglobinuria, Paroxysmal / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides
keywords: bone marrow; cytokines; immunology; inherited bone marrow failure syndromes; monocytes
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