Critical role for granulocyte colony-stimulating factor in inflammatory arthritis.
Granulocyte colony-stimulating factor (G-CSF) is a well known regulator of granulopoiesis, but the role of endogenous G-CSF in inflammatory joint disease has not been explored. We studied the response of G-CSF-deficient mice in experimental models of joint inflammation. We show that G-CSF deficiency protects mice from acute and chronic arthritis. Reduced severity was associated with blunted mobilization of granulocytic cells from the bone marrow and less cellular infiltrate and cellular activation in inflamed joints. We also demonstrate that G-CSF blockade in established collagen-induced arthritis in WT mice markedly reduces disease manifestations and is as effective as tumor necrosis factor blockade. Our results reveal a critical role for G-CSF in driving joint inflammation and highlight G-CSF as a potential therapeutic target in inflammatory joint diseases, such as rheumatoid arthritis.
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia.
Kate E
KE
Lawlor
Ian K
IK
Campbell
Donald
D
Metcalf
Kristy
K
O'Donnell
Annemarie
A
van Nieuwenhuijze
Andrew W
AW
Roberts
Ian P
IP
Wicks
D000208:Acute Disease; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017951:Antigen Presentation / Q000276:immunology; D001169:Arthritis, Experimental / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D002908:Chronic Disease; D024043:Collagen Type II; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000494:pharmacology; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics* / Q000276:immunology*; D006098:Granulocytes / Q000166:cytology; D007375:Interleukin-1 / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains
D000911:Antibodies, Monoclonal; D024043:Collagen Type II; D007375:Interleukin-1; D016179:Granulocyte Colony-Stimulating Factor; D005620:Freund's Adjuvant