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: Ken Matsui, Neelam Giri, Blanche P Alter, Ligia A Pinto
• Journal: British journal of haematology (Br J Haematol) Vol. 163 Issue 1 Pg. 81-92 (Oct 2013) ISSN: 1365-2141 [Electronic] England
• PMID: 23889587 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
• Copyright: © Published 2013. This article is a U.S. Government work and is in the public domain in the U.S.A.

Chemical References

• Cytokines
• Lipopolysaccharides

Topics

• Adolescent
• Adult
• Aged
• Anemia, Aplastic
• Bone Marrow Cells (immunology, metabolism)
• Bone Marrow Diseases
• Bone Marrow Failure Disorders
• Child
• Child, Preschool
• Cytokines (biosynthesis, metabolism)
• Hemoglobinuria, Paroxysmal (immunology, metabolism)
• Humans
• Intracellular Space (metabolism)
• Lipopolysaccharides (immunology)
• Middle Aged
• Monocytes (immunology, metabolism)
• T-Lymphocyte Subsets (immunology, metabolism)
• Young Adult