The colony-stimulating factors and collagen-induced arthritis: exacerbation of disease by M-CSF and G-CSF and requirement for endogenous M-CSF.
There is increasing evidence that the colony-stimulating factors (CSFs) may play a part in chronic inflammatory autoimmune diseases, such as rheumatoid arthritis (RA). We examined the involvement of macrophage CSF (M-CSF or CSF-1) and granulocyte CSF (G-CSF) in collagen-induced arthritis (CIA), a murine model of RA. Daily injections of M-CSF or G-CSF, 20-24 days postprimary immunization with type II collagen, exacerbated disease symptoms in suboptimally immunized DBA/1 mice. Support for the involvement of endogenous M-CSF in CIA was obtained by studies in which neutralizing monoclonal antibody reduced the severity of established CIA and also by studies showing the resistance of M-CSF-deficient op/op mice to CIA induction. These studies show that M-CSF and G-CSF can be proinflammatory in CIA and provide evidence that macrophage- and granulocyte-lineage cells can exacerbate CIA. Our results also show that M-CSF-dependent cells are essential for CIA development, suggesting M-CSF may be a suitable target for therapeutic intervention in RA.
Inflammation Research Centre, The University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, Australia. campbell@wehi.edu.au
I K
IK
Campbell
M J
MJ
Rich
R J
RJ
Bischof
J A
JA
Hamilton
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D001327:Autoimmune Diseases / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology*; D019070:Cell Lineage; D002645:Chickens; D003094:Collagen / Q000276:immunology / Q000633:toxicity; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000633:toxicity*; D006098:Granulocytes / Q000473:pathology; D007113:Immunity, Innate; D007114:Immunization; D007375:Interleukin-1 / Q000633:toxicity; D016173:Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology / Q000633:toxicity*; D008264:Macrophages / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D010022:Osteopetrosis / Q000150:complications / Q000235:genetics; D051381:Rats; D011994:Recombinant Proteins / Q000633:toxicity
D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D016173:Macrophage Colony-Stimulating Factor; D003094:Collagen