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Review

GM-CSF as a target in inflammatory/autoimmune disease: current evidence and future therapeutic potential

Pages 457-465 | Published online: 08 Mar 2015
 

Abstract

Granulocyte-macrophage colony-stimulating factor (GM-CSF) can be viewed as a pro-inflammatory cytokine rather than as a key regulator of steady state and systemic myelopoiesis. Key aspects of GM-CSF biology need to be clarified such as pro-survival vs activation/differentiation function, its cellular sources, its responsive cell populations, its downstream mediators/pathways, and when GM-CSF is relevant. Striking effects of GM-CSF depletion/deletion in some pre-clinical autoimmune/inflammation models have been reported. Systemic effects of administered GM-CSF are not necessarily informative about its local blockade in disease. Recent clinical RA trials, particularly Phase II trials with mavrilimumab (anti-GM-CSFRα Ab), show rapid and impressive efficacy with no significant adverse effects. Larger and longer trials targeting GM-CSF are needed and with careful monitoring of unwanted side effects. This review summarizes the most recent information on these topics.

Financial & competing interests disclosure

JA Hamilton is employed by The University of Melbourne. The University of Melbourne has licensed patented technology relating to therapeutically targeting GM-CSF to MorphoSys AG, Germany. JA Hamilton has consultancies with GSK and CSL Pty Ltd amounting to less than $10,000 per year per entity. This work was supported by a Senior Principal Research Fellowship from the National Health and Medical Research Council of Australia. Rifa Sallay is acknowledged for typing the manuscript. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues
  • Granulocyte macrophage-colony-stimulating factor (GM-CSF) can be viewed as a pro-inflammatory cytokine rather than as a key regulator of steady state and systemic myelopoiesis.

  • Key aspects of GM-CSF biology need to be clarified such as pro-survival versus activation/differentiation function, its cellular sources, its responsive cell populations, its downstream mediators/pathways, and when GM-CSF is relevant.

  • Striking effects of GM-CSF depletion in some pre-clinical autoimmune/inflammation models have been reported.

  • Systemic effects of administered GM-CSF are not necessarily informative about its (local?) blockade in disease.

  • Recent clinical RA trials, particularly Phase II trials with mavrilimumab (anti-GM-CSFR Ab), show rapid and impressive efficacy with no significant adverse effects.

  • Larger and longer trials targeting GM-CSF are needed and with careful monitoring of unwanted side effects.

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