title: 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.
authors.affiliation: Walter &Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Ian P
authors.initials: IP
authors.lastname: Wicks
authors.affiliation: Walter &Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3052, Australia.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Roberts
mesh_terms: D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D007155:Immunologic Factors / Q000627:therapeutic use*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism
chemical_list: D007155:Immunologic Factors; D036341:Intercellular Signaling Peptides and Proteins; D016178:Granulocyte-Macrophage Colony-Stimulating Factor