Blockade of collagen-induced arthritis post-onset by antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF): requirement for GM-CSF in the effector phase of disease

Arthritis Res. 2001;3(5):293-8. doi: 10.1186/ar318. Epub 2001 Jun 11.


There is mounting evidence for a role of the growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in inflammatory disease, including arthritis. In the present study, we examined the effectiveness of treatment of collagen-induced arthritis (CIA) with a neutralizing mAb to GM-CSF. DBA/1 mice were immunized for the development of CIA and treated at different times, and with different doses, with neutralizing mAb to GM-CSF or isotype control mAb. Anti-GM-CSF mAb treatment prior to the onset of arthritis, at the time of antigen challenge, was effective at ameliorating the ensuing disease. Modulation of arthritis was seen predominantly as a reduction in overall disease severity, both in terms of the number of limbs affected per mouse and the clinical score of affected limbs. Importantly, anti-GM-CSF mAb treatment ameliorated existing disease, seen both as a reduction in the number of initially affected limbs progressing and lower numbers of additional limbs becoming affected. By histology, both inflammation and cartilage destruction were reduced in anti-GM-CSF-treated mice, and the levels of tumor necrosis factor-a and IL-1beta were also reduced in joint tissue washouts of these mice. Neither humoral nor cellular immunity to type II collagen, however, was affected by anti-GM-CSF mAb treatment. These results suggest that the major effect of GM-CSF in CIA is on mediating the effector phase of the inflammatory reaction to type II collagen. The results also highlight the essential role of GM-CSF in the ongoing development of inflammation and arthritis in CIA, with possible therapeutic implications for rheumatoid arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Ankle Joint / drug effects
  • Ankle Joint / metabolism
  • Ankle Joint / pathology
  • Antibodies, Blocking / administration & dosage*
  • Antibodies, Monoclonal / administration & dosage
  • Arthritis, Experimental / immunology
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / prevention & control*
  • Cartilage, Articular / drug effects
  • Cartilage, Articular / pathology
  • Collagen / immunology*
  • Disease Models, Animal
  • Dose-Response Relationship, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology*
  • Hindlimb / drug effects
  • Hindlimb / pathology
  • Immunization
  • Interleukin-1 / metabolism
  • Local Lymph Node Assay
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • Mice, Inbred DBA
  • Tumor Necrosis Factor-alpha / metabolism


  • Antibodies, Blocking
  • Antibodies, Monoclonal
  • Interleukin-1
  • Tumor Necrosis Factor-alpha
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Collagen