The colony-stimulating factors and collagen-induced arthritis: exacerbation of disease by M-CSF and G-CSF and requirement for endogenous M-CSF

• Published in: Journal of leukocyte biology Vol. 68; no. 1; pp. 144 - 150
• Main Authors: Campbell, Ian K., Rich, Melissa J., Bischof, Robert J., Hamilton, John A.
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.07.2000
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Arthritis, Rheumatoid - chemically induced; Arthritis, Rheumatoid - complications; Arthritis, Rheumatoid - physiopathology; Autoimmune Diseases - chemically induced; Autoimmune Diseases - complications; Autoimmune Diseases - physiopathology; Cell Lineage; Chickens; Collagen - immunology; Collagen - toxicity; cytokines; Disease Models, Animal; Granulocyte Colony-Stimulating Factor - antagonists & inhibitors; Granulocyte Colony-Stimulating Factor - immunology; Granulocyte Colony-Stimulating Factor - toxicity; Granulocytes - pathology; hematopoiesis; Immunity, Innate; Immunization; in vivo animal models; inflammatory mediators; Interleukin-1 - toxicity; Macrophage Colony-Stimulating Factor - antagonists & inhibitors; Macrophage Colony-Stimulating Factor - immunology; Macrophage Colony-Stimulating Factor - physiology; Macrophage Colony-Stimulating Factor - toxicity; Macrophages - pathology; Male; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Mutant Strains; Osteopetrosis - complications; Osteopetrosis - genetics; Rats; Recombinant Proteins - toxicity; rheumatoid arthritis
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.68.1.144

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.