Targeting GM-CSF in inflammatory diseases

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Targeting GM-CSF in inflammatory diseases

Abstract

Granulocyte-macrophage colony stimulating factor (GM-CSF) is a growth factor first identified as an inducer of differentiation and proliferation of granulocytes and macrophages derived from haematopoietic progenitor cells. Later studies have shown that GM-CSF is involved in a wide range of biological processes in both innate and adaptive immunity, with its production being tightly linked to the response to danger signals. Given that the functions of GM-CSF span multiple tissues and biological processes, this cytokine has shown potential as a new and important therapeutic target in several autoimmune and inflammatory disorders — particularly in rheumatoid arthritis. Indeed, GM-CSF was one of the first cytokines detected in human synovial fluid from inflamed joints. Therapies that target GM-CSF or its receptor have been tested in preclinical studies with promising results, further supporting the potential of targeting the GM-CSF pathway. In this Review, we discuss our expanding view of the biology of GM-CSF, outline what has been learnt about GM-CSF from studies of animal models and human diseases, and summarize the results of early phase clinical trials evaluating GM-CSF antagonism in inflammatory disorders.

  • GM-CSF (granulocyte-macrophage colony stimulating factor) is a multifunctional cytokine that regulates inflammatory responses, including emergency responses in the bone marrow
  • Mice deficient in GM-CSF develop normally, apart from displaying a lung phenotype similar to pulmonary alveolar proteinosis in humans
  • GM-CSF antagonism has beneficial effects in multiple autoimmune and inflammatory preclinical disease models, including inflammatory arthritis and inflammatory disease of the central nervous system
  • A monoclonal antibody specific to GM-CSFRα (GM-CSF ligand-binding α-chain) was well tolerated in early phase clinical trials in rheumatoid arthritis (RA), leading to impressive clinical responses that included rapid pain relief
  • Therapeutic agents targeting GM-CSF signalling are currently undergoing evaluation in a number of diseases, including RA and multiple sclerosis, among others

 

Best Regards:
Veronica Thompson

Journal Manager
Journal of Cytokine Biology
Email:  cytokinebiol@oajoirnal.org