Regulation of systemic and local myeloid cell subpopulations by bone marrow cell-derived granulocyte-macrophage colony-stimulating factor in experimental inflammatory arthritis

Arthritis Rheum. 2011 Aug;63(8):2340-51. doi: 10.1002/art.30354.


Objective: Even though there are clinical trials assessing granulocyte-macrophage colony-stimulating factor (GM-CSF) blockade in rheumatoid arthritis (RA), questions remain as to how GM-CSF acts as a proinflammatory cytokine. The aims of this study on the regulation of arthritis progression by GM-CSF were to determine the source of the GM-CSF, whether there are systemic effects, the changes in synovial tissue leukocyte populations, and the arthritis model dependence on GM-CSF.

Methods: Bone marrow chimeras were used to determine the source of GM-CSF required for the development of collagen-induced arthritis (CIA). The K/BxN serum-transfer model of arthritis was tested in GM-CSF(-/-) mice and using anti-GM-CSF monoclonal antibodies. Cell populations from arthritic mice were assessed by differential staining and flow cytometry.

Results: In the CIA model, GM-CSF produced by bone marrow-derived cells was required for arthritis development. GM-CSF blockade, while ameliorating the development of CIA, was found to have systemic effects, limiting the increase in circulating Ly-6C(high) monocytes and neutrophils. GM-CSF blockade led to fewer synovial macrophages (both Ly-6C(high) and Ly-6C(low)), neutrophils, and lymphocytes. In the absence of GM-CSF, K/BxN serum-transfer arthritis initially developed normally; however, the numbers of Ly-6C(high) monocytes and synovial macrophages (both Ly-6C(high) and Ly-6C(low)) were again reduced, along with the peak disease severity and maintenance.

Conclusion: GM-CSF is a key player in two arthritis models, participating in interactions between hemopoietic cells, both locally and systemically, to control myeloid cell numbers as well as presumably to "activate" them. These results could be useful for the analysis of current clinical trials targeting GM-CSF in patients with RA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / metabolism*
  • Bone Marrow Cells / metabolism*
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism*
  • Mice
  • Mice, Knockout
  • Myeloid Cells / metabolism*


  • Granulocyte-Macrophage Colony-Stimulating Factor