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Br J Haematol. 2013 Oct;163(1):81-92. doi: 10.1111/bjh.12475. Epub 2013 Jul 25.

Cytokine production by bone marrow mononuclear cells in inherited bone marrow failure syndromes.

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  • 1Human Papillomavirus Immunology Laboratory, Science Applications International Corporation (SAIC)-Frederick, Incorporated, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.

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.

© Published 2013. This article is a U.S. Government work and is in the public domain in the U.S.A.

KEYWORDS:

bone marrow; cytokines; immunology; inherited bone marrow failure syndromes; monocytes

PMID:
23889587
[PubMed - indexed for MEDLINE]
PMCID:
PMC3930339
Free PMC Article
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