TNF alpha inhibits SDF-1 increases osteoclast precursors

Rochester, NY -

It is known that inflammatory mediators, such as interferon gamma, under chronic conditions are generally suppressive of hematopoiesis, whereas under acute conditions hematopoiesis is actually enhanced by inflammatory mediators. 

In a recent paper (Zhang et al. TNF inhibits production of stromal cell-derived factor 1 by bone stromal cells and increases osteoclast precursor mobilization from bone marrow to peripheral blood. Arthritis Res Ther 2008;10(2):R37) the effects of chronic TNF-alpha administration on bone marrow SDF-1 production was assessed.  TNF-alpha is of particular interest since this is the agent that when targetted by antibodies induces remission in arthritis (eg think of the efficacy of Remicade), and also is associated with cancer cachexia.

SDF-1 is the chemokine that is secreted at a basal level by the bone marrow stroma which retains hematopoietic stem cells in the bone marrow microenvironment.  Additionally, administration of SDF-1 in other parts of the body results in selective hematopoietic stem cell migration to the area of administration.

The authors of the paper demonstrated:

1. Osteoclast progenitors migrate to SDF-1.

2. TNF-alpha suppresses production of SDF-1 by bone marrow stroma and bone marrow stroma cell lines. 

3. TNF-alpha treatment of mice induces suppression of bone marrow stroma SDF-1 and increased circulation of osteoclastic progenitor cells. 

Thus one question that may come from this study is whether cancer patients with chronic elevation in TNF-alpha may have increased osteoclastic ability, which in turn may promote tumor metastasis to bone !?!?