GM-CSF as a target in inflammatory/autoimmune disease: current evidence and future therapeutic potential.
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.
Department of Medicine, The Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria 3050, Australia.
John A
JA
Hamilton
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D017322:Clinical Trials, Phase II as Topic; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018836:Inflammation Mediators; C561644:mavrilimumab; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
GM-CSF; KB003; MOR103; antibody; inflammation; mavrilimumab; namilumab; rheumatoid arthritis