title: Granulocyte colony-stimulating factor (G-CSF) plays an important role in immune complex-mediated arthritis.
abstract: Neutrophils are an abundant cell type in many chronic inflammatory diseases such as rheumatoid arthritis (RA); however, their contribution to the pathology of RA has not been widely studied. A key cytokine involved in neutrophil development and function is granulocyte-colony stimulating factor (G-CSF). In this study we used the K/BxN serum-transfer arthritis (STA) model, mimicking the effector phase of RA, to investigate the importance of G-CSF in arthritis development and its relation to neutrophils. Here, we show for the first time in this model that G-CSF levels are increased both in the serum and in inflamed paws of arthritic mice and importantly that G-CSF blockade leads to a profound reduction in arthritis severity, as well as reduced numbers of neutrophils in blood. Moreover, CXCL1 and CXCL2 levels in the arthritic joints were also lowered. Our data demonstrate that G-CSF is a pivotal driver of the disease progression in the K/BxN STA model and possibly acts in part by regulating neutrophil numbers in the circulation. Therefore, our findings suggest that G-CSF might be a suitable target in RA, and perhaps in other immune complex-driven pathologies.
authors: Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.|Novo Nordisk A/S, Måløv, Denmark.
authors: Anne D
authors: AD
authors: Christensen
authors: Novo Nordisk A/S, Måløv, Denmark.
authors: Claus
authors: C
authors: Haase
authors: Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
authors: Andrew D
authors: AD
authors: Cook
authors: Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
authors: John A
authors: JA
authors: Hamilton
mesh_terms: D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology* / Q000503:physiopathology*; D054360:Chemokine CXCL1 / Q000276:immunology; D054426:Chemokine CXCL2 / Q000276:immunology; D004195:Disease Models, Animal; D018450:Disease Progression; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood / Q000276:immunology*; D006801:Humans; D007596:Joints / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000276:immunology
chemical_list: D000936:Antigen-Antibody Complex; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D016179:Granulocyte Colony-Stimulating Factor
keywords: Chemokines; G-CSF; Immune-complex driven arthritis; K/BxN serum-transfer arthritis model; Neutrophils