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 Blood, 1 May 2004, Vol. 103, No. 9, pp. 3349-3354.
Prepublished online as a Blood First Edition Paper on December 30, 2003; DOI 10.1182/blood-2003-10-3438.

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Submitted October 7, 2003
Accepted December 19, 2003

Interleukin-6 deficiency affects bone marrow stromal precursors resulting in defective hematopoietic support

Maria del Carmen Rodriguez, Antonio Bernad, and Miguel Aracil*

Inmunologia y Oncologia, Centro Nacional de Biotecnologia, Madrid, Spain

* Corresponding author; email: maracil{at}cnb.uam.es.

Interleukin-6 (IL-6) is a critical factor in the regulation of stromal function and hematopoiesis. In vivo bromodeoxyuridine incorporation analysis indicates that the percentage of Lin-Sca-1+ hematopoietic progenitors undergoing DNA synthesis is diminished in IL-6-deficient (IL-6-/-) bone marrow (BM) compared to wild-type BM. Reduced proliferation of IL-6-/- BM progenitors is also observed in IL-6-/- long-term bone marrow cultures, which show defective hematopoietic support as measured by production of total cells, granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E). Seeding experiments of wild-type and IL-6-/- BM cells on irradiated wild-type or IL-6-deficient stroma indicate that the hematopoietic defect can be attributed to the stromal and not to the hematopoietic component. In IL-6-/- BM, stromal mesenchymal precursors, fibroblast-CFU (CFU-F) and stroma-initiating cells (SIC) are reduced to almost 50% of the wild-type BM value. Moreover, IL-6-/- stroma show increased CD34 and CD49e expression and reduced expression of the membrane antigens VCAM-1, Sca-1, CD49f and Thy.1. These data strongly suggest that IL-6 is an in vivo growth factor for mesenchymal precursors, which are in part implicated in the reduced longevity of the long-term repopulating stem cell compartment of IL-6-/- mice.


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