Dual Role of GM-CSF as a Pro-Inflammatory and a Regulatory Cytokine: Implications for Immune Therapy

J Interferon Cytokine Res. 2015 Aug;35(8):585-99. doi: 10.1089/jir.2014.0149. Epub 2015 Mar 24.


Granulocyte macrophage colony stimulating factor (GM-CSF) is generally recognized as an inflammatory cytokine. Its inflammatory activity is primarily due its role as a growth and differentiation factor for granulocyte and macrophage populations. In this capacity, among other clinical applications, it has been used to bolster anti-tumor immune responses. GM-CSF-mediated inflammation has also been implicated in certain types of autoimmune diseases, including rheumatoid arthritis and multiple sclerosis. Thus, agents that can block GM-CSF or its receptor have been used as anti-inflammatory therapies. However, a review of literature reveals that in many situations GM-CSF can act as an anti-inflammatory/regulatory cytokine. We and others have shown that GM-CSF can modulate dendritic cell differentiation to render them "tolerogenic," which, in turn, can increase regulatory T-cell numbers and function. Therefore, the pro-inflammatory and regulatory effects of GM-CSF appear to depend on the dose and the presence of other relevant cytokines in the context of an immune response. A thorough understanding of the various immunomodulatory effects of GM-CSF will facilitate more appropriate use and thus further enhance its clinical utility.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use
  • Autoimmune Diseases / drug therapy
  • Autoimmunity
  • Cytokines / pharmacology
  • Cytokines / physiology*
  • Cytokines / therapeutic use
  • Drug Evaluation, Preclinical
  • Granulocyte-Macrophage Colony-Stimulating Factor / pharmacology
  • Granulocyte-Macrophage Colony-Stimulating Factor / physiology*
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Humans
  • Immune Tolerance
  • Immunosuppressive Agents / metabolism
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Immunotherapy
  • Inflammation / drug therapy
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation Mediators / pharmacology
  • Inflammation Mediators / physiology*
  • Inflammation Mediators / therapeutic use


  • Anti-Inflammatory Agents
  • Cytokines
  • Immunosuppressive Agents
  • Inflammation Mediators
  • Granulocyte-Macrophage Colony-Stimulating Factor